Azo pigments and quinacridones induce delayed hypersensitivity in

COD
Contact Dermatitis • Original Article
Contact Dermatitis
Azo pigments and quinacridones induce delayed hypersensitivity
in red tattoos
Sophie Gaudron1 , Marie-Christine Ferrier-Le Bouëdec1 , Frederic Franck2 and Michel D’Incan1
1 Department of Dermatology, Université d’Auvergne, CHU Clermont-Ferrand Hôpital Estaing, Lucie et Raymond Aubrac, 63003 Clermont-Ferrand, France
and 2 Department of Pathology, Université d’Auvergne, CHU Clermont-Ferrand Hôpital Estaing, Lucie et Raymond Aubrac, 63003 Clermont-Ferrand, France
doi:10.1111/cod.12317
Summary
Background. Induction of delayed hypersensitivity reactions by red tattoos has been
occasionally reported. Little is known about the inks used. Azo pigments have been
implicated in some instances, but there is only one reported case involving quinacridones.
Objectives. To describe the clinical and pathological features and outcome of skin
reactions induced by red tattoo pigments.
Patients, materials, and methods. Six patients with a cutaneous reaction induced by
a red tattoo pigment underwent biopsy and prick and patch testing with the inks supplied.
Results. We observed seven reactions in the 6 patients. Histology showed various patterns: three lichenoid, two eczematous, and two pseudolymphomatous. Five reactions
occurred with azo pigments, and two with quinacridones, in both cases with Violet 19
and Red 122. Four inks were tested. Only one patch test gave a positive result at a late
reading (day 7). Prick tests gave negative results. The reactions required various treatments, including laser treatment for 2 patients. Activation of the reaction in 1 case was
transient.
Conclusion. Azo pigments and quinacridones both triggered reactions with similar
clinical aspects but with varying histological findings. Patch and prick test results were
disappointing with both. Reactions occurred following laser use in 1 case.
Key words: azo dye; hypersensitivity; patch testing; quinacridone; red tattoo.
Tattoos have become increasingly popular worldwide.
Several years ago, most hypersensitivity cases were
related to mercury-derived pigments, but pigments have
changed, and organic pigments are now more commonly
found. In this article, we report the clinical and histological features of 6 patients who had skin reactions
induced by red tattoos. We pay particular attention
to the pathological features and the difficulties in skin
testing.
Correspondence: Sophie Gaudron, Department of Dermatology,
Auvergne University CHU Estaing, 1 Place Lucie et Raymond Aubrac,
63003 Clermont-Ferrand Cedex 1, France. Tel: +33687365907; Fax:
+33473750552. E-mail: [email protected]
Conflict of interests: The authors declare no conflict of interests.
Accepted for publication 14 October 2014
© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Contact Dermatitis, 72, 97–105
Materials and Methods
Patients and materials
We report the cases of 6 patients (4 females and 2 males)
referred by dermatologists between 2010 and 2013 to
the allergology and dermatology clinic of the university
hospital of Clermont-Ferrand, France, for cutaneous reactions at the red sites of polychromatic tattoos. Two were
multi-tattooed (patients 1 and 5).
The medical histories and clinical features were
recorded, and pictures were taken in each case.
The patients denied any history of allergy, atopic disorders, or other skin diseases, except for 1 (patient 5) who
had a history of contact dermatitis of unknown origin.
Biopsies of inflamed skin were taken, stained with
haematoxylin and eosin, and then stained with a panel of
lymphocyte-specific antibodies.
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REACTION TO RED TATTOOS • GAUDRON ET AL.
We acquired data sheets with detailed compositions of
the inks from the manufacturers, and asked the tattooists
to supply samples of the inks used for cutaneous testing.
Methods
Epicutaneous tests were performed with the inks supplied
without dilution.
Patch tests with the European baseline series, metal
series and a textile dyes series (Chemotechnique Diagnostics, Vellinge, Sweden) were also performed with Finn
Chambers® on Scanpor® tape (SmartPractice, Phoenix,
AZ, USA) with a 2-day occlusion. Skin reactions were
assessed after 2, 4 and 7 days, according to International
Contact Dermatitis Research Group criteria.
Prick testing on the inner sides of the patients’ left
forearms was also performed with undiluted inks, and
skin reactions were assessed after 20 min, 2 days, and
4 days.
Patients were followed up and treated with topical
corticosteroids (clobetasol propionate cream under occlusion) or intralesional corticosteroids (triamcinolone acetonide). When the reaction was persistent, treatment with
a Q-switched 532-nm Nd:YAG laser was proposed. Patient
consent was obtained after a full explanation of possible
complications.
Results
Clinical presentation
The 6 patients developed seven skin reactions, from
2 weeks to 3 years after having a red tattoo. One patient
(patient 5) had a reaction in two different tattoos, one of
which had been performed 2 months previously and the
other 4 months previously, with two different red inks.
All patients had similar presentations, with pruritus,
swelling and discomfort in the red portions of their polychromatic tattoos (Fig. 1a, b). The reaction was papular
with some crusting.
Biopsy results
For all 6 patients, biopsy specimens of the swollen red
areas were examined. In 3 patients (1–3), biopsy showed
a lichenoid reaction, with a band-like dense lymphocytic infiltrate in the upper dermis and necrotic basal
keratinocytes. In 2 patients (4, 5), it showed a pseudolymphomatous reaction: a dermal infiltrate of small to
medium-sized CD4+ T cells expressing T follicular helper
markers (CD10, CXCL13, Bcl6, and PD1), indicative of
a T follicular helper pseudolymphomatous reaction, in
patient 3 (Fig. 2), and a T cell pseudolymphomatous
98
Fig. 1. Inflammation on red tattoo of the leg: (a) patient 1;
(b) patient 5 (reaction 6).
reaction with a dense nodular lymphoid infiltrate of small
to medium-sized lymphocytes in the reticular dermis,
with intermingled pigment deposits, in patient 4. In the
latter patient, the lymphoid infiltrate was mainly composed of mature CD3+ , CD4+ and CD5+ T lymphocytes.
Bcl6 was strongly expressed. B lymphocyte markers were
negative. Patient 5 had an eczematous reaction to both
tattoos.
Involved inks
From the information provided by the tattooists, we were
able to obtain the names of the manufacturers and the
names and compositions of the inks involved in the seven
skin reactions. In five lesions, the colorants used were azo
pigments, and in the other two they were quinacridones
(Table 1). The trade names of the azo pigments used were
as follows: BRIGHT RED (tattoo reaction 1), a mixture
of three azo pigments, Red 210 (CI 12 477), Yellow 65
(CI 11 740), and Orange 13 (CI 21 110); RASPBERRY
(tattoo reaction 2), Red 63:1 (CI 15 880); LIGHT RED,
DEEP RED, and DARK RED (tattoo reaction 3), all three
corresponding to Red 170 (CI 12 475); FLAME RED
(tattoo reaction 4), Red 112 (CI 12 370); and LIGHT RED
(tattoo reaction 5), Red 170 (CI 12 475) (Table 2). The
trade names of the quinacridone pigments used were as
follows: TRUE MAGENTA (tattoo reaction 6), a mixture of
two quinacridones, Violet 19 (CI 73 900) and Red 122 (CI
73 915); and DEEP PURPLE and DEEP MAGENTA (tattoo
reaction 7), a mixture of the same two quinacridones,
Violet 19 and Red 122 (Table 2). These inks, in addition
to organic pigments, contained water, glycerol, and isopropyl alcohol, and some of them contained titanium
dioxide, acrylic resin, food-grade gum, phospholipids,
© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Contact Dermatitis, 72, 97–105
REACTION TO RED TATTOOS • GAUDRON ET AL.
Fig. 2. Patient 3:
pseudolymphomatous reaction
with a T helper follicular
phenotype. Hematoxylin Eosin
Safran (HES).
food grade emulsifier, dimethylcarbinol, and witch hazel,
according to the Material Safety Data Sheets. There was
no mention of preservatives in the composition of the inks
supplied by the manufacturers.
Patch and prick tests
An ink sample was available for only four reactions from
3 patients, and was patch and prick tested.
Of the 5 patients with reactions to azo pigments, two
were patch and prick tested: patch tests with the inks
gave negative results, except for patient 1, in whom a +
reaction was seen on day 7. Patient 5 (tattoo reaction 5)
showed ++ reactions to nickel sulfate, potassium dichromate, and cobalt chloride, and a + reaction to fragrance
mix 1. Patch tests with metal series including mercury
and textile dyes series gave negative results. Prick tests
gave negative results (Table 2).
Both patients with reactions to quinacridones were
tested: patch and prick tests with the undiluted inks used
gave negative results. The results of patch tests with the
European baseline series, metal series and textile dyes
series for patient 5 (tattoo reaction 6) are mentioned
above, and patient 6 showed a + reaction to nickel sulfate
(Table 2).
Treatment
All of the patients were treated with potent topical
corticosteroids (clobetasol propionate 0.05% cream),
© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Contact Dermatitis, 72, 97–105
applied daily under occlusion. Patients 1 and 6 received
intralesional triamcinolone. These treatments had only
transient efficacy. Subsequently, and because the reaction was very disfiguring, patients 1 and 3 required and
accepted Q-switched 532-nm Nd:YAG laser courses.
Patient 1 had six courses at 2-weekly intervals in a wide
red tattoo. He experienced a severe reaction of the entire
lower limb with an initial oedematous erythema, followed
by superficial erosion and crust formation that took
2 weeks to heal (Fig. 3a). Curiously, he also suffered a new
pruritic and oedematous attack during laser treatment in
two distant red tattoos that had been performed several
years before but that, initially, were free of any clinical
reaction (Fig. 4a, b). These secondary reactions were
persistent after the use of topical corticosteroids. Laser
treatment was then performed, with no activation of the
allergic reaction and no relapse after 2 years of follow-up.
Pigmentation disorders, however, remained (Fig. 3b).
Patient 3 required only two laser sessions.
Discussion
Polychromatic tattoos are now popular worldwide. However, the frequency of delayed reactions to red tattoos is
unknown. Information in the literature is scarce, and only
a few individual cases and four small series have been documented (1, 2, 4, 5).
The time to the development of a tattoo ink reaction seems to be extremely variable from one patient to
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REACTION TO RED TATTOOS • GAUDRON ET AL.
Table 1. Pigments used in tattooed patients
Pigment Red 210 (CI 12 477)a
Reaction mass of 4-{[4-(aminocarbonyl)phenyl]azo}-3-hydroxy-N(2-methoxyphenyl)naphthalene-2-carboxamide and
4-{[4-(aminocarbonyl)phenyl]azo}-N-(2-ethoxyphenyl)-3-hydroxynaphthalene2-carboxamide
Pigment Yellow 65 (CI 11 740)b
2-[(4-Methoxy-2-nitrophenyl)azo]-N-(2-methoxyphenyl)-3-oxo-butyramide
Pigment Orange 13 (CI 21 110)b
4,4′ -{[3,3′ -Dichloro(1,1′ -biphenyl)-4,4′ -diyl]bis(azo)}bis(2,4-dihydro5-methyl-2-phenyl-3H-pyrazol-3-one)
Pigment Red 63:1 (CI 15 880)b
Calcium 3-hydroxy-4-[(1-sulphonato-2-naphthyl)azo]-2-naphthoate
Pigment Red 170 (CI 12 475)b
4-{[4-(Aminocarbonyl)phenyl]azo}-N-(2-ethoxyphenyl)-3-hydroxynaphthalene2-carboxamide
Pigment Red 112 (CI 12 370)b
3-Hydroxy-N-(2-methylphenyl)-4-[(2,4,5-trichlorophenyl)azo]naphthalene2-carboxamide
Pigment Violet 19 (CI 73 900)b
5,12-Dihydroquino(2,3-b)acridine-7,14-dione
Pigment Red 122 (CI 73 915)b
5,12-Dihydro-2,9-dimethylquino(2,3-b)acridine-7,14-dione
a From http://www.dyestuffintermediates.com
b From http://www.chemblink.com
another. In our series, reactions to azo pigments containing inks occurred from 15 days to 3 years after tattooing. In other reports, reaction times have ranged from
a few weeks to a few months. In our patients, reactions
to quinacridone pigments occurred from 2 to 4 months
after tattooing. The reaction to quinacridone described by
Greve occurred 4 weeks after tattooing (6). In addition,
5 cases of late reactions (after several years) have been
reported with inorganic pigments and inks of unknown
composition (3, 7–9). One of our patients had an early
reaction (2 weeks). This suggests rapid sensitization by the
tattoo procedure or previous sensitization to a related pigment. However, this multi-tattooed patient experienced
no reaction or other dye contact dermatitis. The 5 other
patients had more delayed reactions, from 2 months to
3 years. This time lag could be attributable to several
100
different mechanisms, such as acquired hypersensitivity
to the pigment or a tolerance breakdown. The allergens
might have been formed by chemical changes in pigment
molecules through haptenization in the skin weeks or
months after tattooing.
The clinical presentation was similar in our patients,
with a pruritic papular reaction and slight crusting
restricted to the red areas of the polychromatic tattoos.
However, as in other studies, histology patterns were
slightly different (2, 3, 6, 7, 10–12). We observed two
lichenoid reactions, two pseudolymphomatous reactions and one eczematous reaction with the azo dyes,
and one eczematous and one lichenoid reaction with
quinacridones. As reported elsewhere, the lichenoid
pattern is commonly observed (2, 3, 7, 8, 13, 14). In
contrast, there are few reports of pseudolymphomatous
© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Contact Dermatitis, 72, 97–105
reaction
© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Contact Dermatitis, 72, 97–105
2
3
4
5
2
3
4
5
44
40
30
35
7
6
28
44
F
M
M
F
F
F
M
Sex
Back
Leg
Back
Chest
Forearm
Ankle
Leg
site
Tattoo
Histology
Ink manufacturer
Trade name
Pigments
Colour
2 months
4 months
2 months
3 years
3 months
2 months
15 days
reaction onset
Lichenoid
Eczematous
Eczematous
Pseudolymphomatous
reaction
Pseudolymphomatous
reaction
Lichenoid
Lichenoid
Starbrite (Somers, CT,
USA)
Intenze (Rochelle
Park, NJ, USA)
Eternal (Brighton, MI,
USA)
Azayaka (Riccione,
Italy)
Eternal (Brighton, MI,
USA)
Starbrite 2 (Somers,
CT, USA)
Intenze (Rochelle
Park, NJ, USA)
Red 122
DEEP MAGENTA
CI 73 915
CI 73 915
CI 73 900
Red 122
Violet 19
CI 73 900
CI 12 475
CI 12 370
CI 12 475
Violet 19
Red 170
Red 112
Red 170
CI 15 880
CI 21 110
Red 63:1
CI 11 740
Yellow 65
CI 12 477
index
Orange 13
Red 210
DEEP PURPLE
TRUE MAGENTA
LIGHT RED
FLAME RED
DARK RED
DEEP RED
LIGHT RED
RASPBERRY
BRIGHT RED (Mario
Barth Gold label)
(distributor)
−
EBS
Ni +
Ni ++, Cr ++,
Co ++,
fragrance mix
1+
Ni ++, Cr ++,
Co ++,
fragrance mix
1+
ND
ND
ND
−
−
−
ND
ND
ND
−
series
Metal
−
−
−
ND
ND
ND
−
dye series
Textile
Undiluted
−
−
−
ND
ND
ND
+ D7
ink
−
−
−
ND
ND
ND
−
inks
undiluted
with
tattoo and
tests
Prick
between
Patch tests
Interval
EBS, European baseline series; F, female; M, male; ND, not done; −, negative.
6
5
Reactions to quinacridones
1
1
49
(years)
Age
Reactions to azo dyes
Patient
Tattoo
Table 2. Patient characteristics
REACTION TO RED TATTOOS • GAUDRON ET AL.
101
REACTION TO RED TATTOOS • GAUDRON ET AL.
Fig. 3. Patient 1: (a) severe focal reaction during laser treatment;
(b) after six laser sessions.
Fig. 4. Patient 1, distant polychromatic tattoo: (a) before laser
treatment; (b) reaction after laser treatment on the other leg.
reactions (3, 6, 15, 16). Two of our patients showed
pseudolymphomatous reactions in response to red tattoos with azo pigments, including one T helper follicular
(THF) cutaneous proliferation. Cutaneous THF proliferations were recently described by Battistella et al. (17).
To our knowledge, there are no documented reports of
pseudolymphomatous reactions with a THF phenotype
to red tattoo pigment. Histological patterns did not help
in solving the cases. These polymorphic histological
patterns indicate the complexity of the pigment reactions
and the different pathomechanisms involved. The main
use of biopsies is to exclude differential diagnoses, such as
infectious diseases.
Showing tattoo ink and colorant allergy by skin tests is
difficult. We obtained the details and compositions of the
inks used in all of our patients, but only four samples of
102
ink. In three of the four published series reporting delayed
reactions to red tattoos, there were no details of the inks
or colorants used, and in only one series were the inks
tested (1). This illustrates the difficulty in obtaining ink
details and samples. Of the 15 patients mentioned in the
literature who had patch tests with the inks, only 5 had
positive results (8, 10, 11, 18, 19). Most authors mention the low sensitivity of the epicutaneous tests, which
is probably attributable to the poor penetration into the
skin of the applied ink. Patch testing yielded disappointing results in our cases, as in other studies (1, 6, 12,
14–16, 20). However, 1 of our patients had a reaction at
D7 after patch testing, which suggests that delayed test
reading can be useful. One other author reported a late
reaction, at D8 (8). A negative patch test result does not,
however, rule out pigment as a cause. Recently, Serup
et al. patch tested 90 patients with non-infectious chronic
tattoo reactions, with batteries of baseline allergens, disperse dyes/textile allergens, and a selection of tattoo ink
products. The tests gave negative results. The authors suggested that the responsible allergen is not present directly
in the tattoo ink, but results from chemical changes in the
pigment molecule, perhaps weeks or months after tattooing, which would explain why the patch tests gave negative results (21).
Prick tests were performed in only two studies, and
only Wenzel et al. reported positive prick test results: skin
reactions were evaluated after 4 days in 3 patients with
colorants used to make cosmetic tattoos (1). In the 3
patients (four inks) we tested, prick tests gave negative
results. Perhaps a later reading would be useful.
Intradermal testing should have been more suitable,
as the hypersensitivity reaction was caused by intracutaneous rather than epicutaneous challenge. However,
intradermal tests carry the risk of long-lasting skin reactions, and for this reason most authors do not recommend
them (12, 14). Likewise, we preferred not to perform
intradermal tests. Intradermal testing has been reported
in only two studies: in one the test gave a positive result
with undiluted ink (15), and in the other only aluminium
was tested, and was positive (22).
Metal particles are sometimes reported to be responsible for red tattoo reactions, especially nickel sulfate and
mercury sulfide (cinnabar) (10, 18). Although the colorants used in our patients were organic pigments that,
according to the manufacturers, contained no metals,
we cannot exclude the possibility that they were, in fact,
contaminated. Mercuric sulfide is now being replaced by
organic pigments, chiefly azo pigments.
Most of the patients in our series reacted to red inks
containing azo pigments, in two instances Red 170, as in a
previous report (14). Azo pigments belong to a wide class
© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Contact Dermatitis, 72, 97–105
REACTION TO RED TATTOOS • GAUDRON ET AL.
of synthetic organic pigments that have the nitrogen azo
group N=N as part of their molecular structure. They give
bright, high-intensity colours. More than half of all marketed dyes used in textiles, inks, paint and plastics are azo
dyes. Because of structural similarities, cross-sensitization
between azo pigments and para-amino compounds may
occur (23). Hence, patients who experience an allergy to
an azo pigment in a tattoo may also be at risk of reactions to everyday products and textiles. Bhardwaj et al.
reported the case of a man who developed a reaction to
a red tattoo that was successfully treated with a CO2 laser.
Six months later, he experienced a reaction after wearing
a red T-shirt. Patch tests with the tattoo colorants and
T-shirt dye showed strong positivity (++) in the previously
affected area (19). To date, none of our patients has had
other reactions, and patch tests with p-phenylenediamine
and textile dyes series have all given negative results.
Like azo pigments, quinacridones are light-fast pigments that are used not only in tattoos but also in paints,
printing inks, and plastics. They may be associated with
azo pigments in red tattoo inks. Bendsoe et al. reported the
first case, in 1991, of a patient with a reaction to an ink
containing azo pigment and quinacridone (24). To our
knowledge, there is only 1 published case of a reaction to
quinacridone Red 122 (CI 73 915) pigment (6).
In the present series, we report 2 new cases of reactions to red tattoos with inks containing quinacridones,
both involving a mixture of two pigments, Violet
19 (CI 73 900) and Red 122 (CI 73 915), that provide
confirmation of the potential involvement of quinacridone
pigments in hypersensitivity reactions to red tattoos.
We observed reactions in patient 5 in two different
tattoos, with the two types of pigment. Cross-sensitization
between azo pigments and quinacridones is unlikely,
owing to the absence of chemical similarities, but
the reactions may have been attributable to common
metabolites produced in the skin, possibly by natural light
exposure.
We were unable to identify the allergens involved
in our patient reactions. As the skin reactions were
restricted to the red areas of the multi-coloured tattoos,
we assumed that the culprit allergens were the red pigment and, more specifically, its metabolites. Moreover,
other ingredients listed by the manufacturers were the
same in other colours. No preservatives were mentioned
in the Material Safety Data Sheet enclosed with each ink.
In spite of the rarity of positive patch test reactions in
other reports, all authors agree in considering colorants
to be the causal allergens (3, 6, 7–14). However, the
responsibility of other compounds, such as impurities,
metal particles, and decomposition products of the inks,
cannot be excluded. There are no published data on the
© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Contact Dermatitis, 72, 97–105
decomposition products of quinacridones. It has been
shown that the concentration of azo pigments in the
skin decreases with time: the pigments are, in part,
transported away via the lymphatic system, and in
part decomposed in the skin into products, including
amino-naphthol-AS and naphthol-AS (25), that could
be responsible for adverse reactions. In the literature to
date, however, no tests have been performed with these
decomposition products. We performed patch tests with
naphthol-AS in 3 of our patients, with negative results.
It has also been shown that exposure of an azoid, Pigment Red 22, to broadband ultraviolet (UV) B radiation
and natural sunlight leads to the formation of the same
decomposition products (26, 27). Some authors have
described cases worsened by sun exposure (3, 14, 15). In
a study of 154 patients with tattoo reactions, 58% were
sun-induced, and lasted from hours to days (28). None
of our patients noticed any change after sun exposure
or complained of worsening, but photoproducts may
have been involved in the reaction. We did not perform
photo patch testing, because we had no more ink material
available. Photo-patch testing with the ink has been mentioned in only two studies, in patients in whom reactions
followed sun exposure and for both of whom the tests
gave negative results (8, 14).
Our patients experienced severe and long-lasting
pruritus. Reduced quality of life was recently reported
in patients with tattoo reactions (29), and treatment is
difficult. In our series, as elsewhere, treatment with a
potent topical steroid and intralesional triamcinolone
was unsuccessful (3, 7, 8, 13, 30). Pulsed laser therapy
is effective in removing tattoos by selectively blasting
the pigment free into the dermis, which is then secondarily removed by macrophages (4, 20, 31). With
their consent, 2 of our patients, for whom topical and
intralesional corticosteroids were ineffective, were treated
with a Q-switched 532-nm Nd:YAG laser. Laser therapy
is controversial, because of the toxicity of photoproducts and the risk of worsening the reaction. Vasold et al.
showed that laser light decomposes the azo pigments into
hazardous products, such as 2-methyl-5-nitroaniline, a
mutagen substance, 4-nitrotoluene, which has a genotoxic potential, 1,4-dichlorobenzene, 2,5-dichloroaniline,
and methoxy-naphthol-AS (32). One of our patients
(patient 1) had a severe reaction during laser treatment.
Local and generalized reactions after laser treatment for
tattoo removal have been imputed to local or systemic
diffusion of pigment (33–35). In our patient, however, in
addition to a local reaction, inflammation restricted to the
red areas in two distant tattoos was observed. This local
distant reaction in the absence of a generalized reaction
cannot be explained by systemic diffusion of the allergen.
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REACTION TO RED TATTOOS • GAUDRON ET AL.
Only one article has reported a reaction in a distant
tattoo during laser removal of another asymptomatic
tattoo (36). The mechanism of this distant activation was
unknown. Vasold and Engel showed that UV light, sunlight and laser radiation of azo pigments can induce the
production of the same photoproducts (26, 27, 32). We
surmised that laser irradiation of the tattoo on the left leg
of our patient resulted in local induction of a large amount
of photoproducts with enhancement of T specific lymphocytes that, after systemic diffusion, reacted in the red
areas of other tattoos on the right leg and the left shoulder
against similar photoproducts that were locally induced
by sunlight UV. The reactions observed in our patient support the idea that the allergen could be produced by natural light exposure and even faster by intense laser light.
The use of lasers for treating tattoo reactions is controversial, surgery should be proposed when topical and
intralesional corticosteroids are ineffective on tattoo
hypersensitivity reactions. Excision is limited to very
small tattoos, because of the risk of scarring. Dermatome
shaving of tattoo reactions can be an effective alternative, with acceptable cosmetic results (37, 38), but it is
important for all of the pigment to be removed.
There is a lack of legislation concerning tattoo products. The Council of Europe made recommendations,
updated in 2008 (ResAP), for governments of the
member states concerning the requirements and criteria for the safety of tattoos and permanent makeup
(39). In France, legislation has been passed on the
basis of the 2008 ResAP resolution. Tattoo and permanent makeup products must not contain or release
certain listed aromatic amines, other substances that
are prohibited in the composition of cosmetic products,
and carcinogenic, mutagenic and reprotoxic substances.
They must comply with the maximum allowed concentrations of impurities. In addition, like capillary dyes,
they must not contain substances recognized to be
sensitizing (40).
Three pigments used in our patients, Violet 19, Red
112 and Red 63, are on the list of the substances that tattoo and permanent make-up products should not contain.
In France, there is also now a national vigilance system for
monitoring the risk of side-effects resulting from the use of
tattoo inks (41).
Conclusion
Reactions to tattoos are long-lasting and difficult to treat.
They require special monitoring to identify the substances
responsible, and patients need to be followed up to detect
new reactions to colorants and inks.
Our observations provide further evidence for the
involvement of azo pigments and quinacridone metabolites and photoproducts in hypersensitivity reactions to
tattoos. Epicutaneous tests are not predictive, so patients
who wish to have new tattoos should be informed of the
risk of recurrence.
Acknowledgements
The authors thank Drs Dominique Delalleau, Isabelle
Gouyon, Isabelle Masson, Hugues Roger, Magali Salavert
and Eric Tisserand for their collaboration, and Mr Jeffrey
Watts for his technical assistance.
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