Tattoo reaction indicating cutaneous sarcoidosis

Case HISTORY
Tattoo reaction indicating
cutaneous sarcoidosis
Carrie Wingfield
This case study discusses the diagnosis and management of a 35-year-old man referred to a dermatology
community clinic with multiple pruritic raised lesions located in all areas of red tattoo pigment. The
histopathology results following punch biopsy describe florid sarcoid granulomas as either local reaction
or indicating systemic sarcoidosis. The variability of a delayed tattoo reaction is considerable with red dye
pigment identified as the most common cause. Sarcoid is an uncommon occurrence in this type of delayed
hypersensivity. The conclusion suggests that this was not a suitable referral for a primary care dermatology
clinic and summarises the appropriate investigations and management associated with the diagnosis.
Key words
Red dye tattoo reaction
Sarcoidosis
Delayed reaction
Introduction
Tattooing remains a popular cultural
practice arguably dating back to
12,000 BC. Historically, tattoos have
been used as a symbolism for marks
of status, rites of passage, religious
and spiritual following, punishment,
ownership, slavery and circus freaks,
to name but a few. Today their use is
more decorative, cosmetic and for
entertainment, although some cultural
use is still very much in evidence
(Gilbert, 2001). History depicts
tattooing as mainly limited to men
such as sailors and the armed forces,
however, the practice is increasingly
observed in modern-day women
(Tanzi, Michael, 2009).
usually resolves 2-3 weeks post
procedure; localised secondary
infection is not unreported and these
days seldom serious. There is evidence
— although improved protocol and
techniques have lowered the risk —
of the transmission of hepatitis, HIV,
tuberculosis, leprosy and syphilis from
previously-used infected needles. Viral
warts and molluscum contagiosum
can also be inoculated from person to
person if the same needle is reused
(Baxter et al, 1993, Miller et al, 1994).
Adverse reactions to tattoos
can vary and can include acute
inflammatory responses as a direct
result of the physical trauma. This
From a dermatology aspect there
is evidence that other cutaneous
conditions apart from sarcoidosis
show a penchant for tattooed skin.
The presentation in the tattoo may
represent the beginning of a skin
disease or accentuation of an existing
condition. Koebner phenomenon is
seen with tattooed skin in conditions
such as psoriasis and lichenoid
reactions. Contact dermatitis from
temporary tattoos, such as henna, is
not uncommon (Wen-Hung Chung
et al, 2002). This variety of other
cutaneous presentations will not be
discussed in the context of this case
study but are listed in Table 1 for
reference.
Carrie Wingfield is Clinical Lead Senior Nurse
Manager in the Dermatology Department,
Norfolk and Norwich University Hospital
The most commonly reported
reaction is an allergic sensitivity to
one of the dye pigments. This can
present in variable forms. Sowden
32
Table 1
Cutaneous disorders manifesting
in tattoos
 Lichen planus
 Psoriasis
 Erythema nodosum
 Lupus erythematous
 Verrucae/molluscum contagiosum
 Melanoma
 Keratoacanthoma
 Contact dermatitis
 Photo-aggravated
 Perforating granuloma annulare
 Pseudolymphoma
et al (1991, 1992) identify Cinnabar
(red) (mercuric sulphide) as the
most common pigment to cause
a reaction and is particular to this
case study. Histological findings for
this type of reaction can range from
contact dermatitis, lichen planus,
‘pseudolymphoma’ and perforating
granuloma annulare.
Sarcoidal reactions in red dye
tattoos are sometimes seen described
as non-specific in many cases following
investigations, although it could
reflect a manifestation of sarcoidosis
in some patients and have been
associated with uveitis as an isolated
finding. Uveitis is an inflammatory eye
condition that may occur alone or it
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Case HISTORY
Figure 1. Case study. Left arm: raised, welldemarcated area.
Figure 2. Case study. Left arm.
Figure 3. Case study. Close-up of lesion on
upper back.
The most commonly
reported reaction is an
allergic sensitivity to one
of the dye pigments.
Sowden et al (1991, 1992)
identify Cinnabar (red
mercuric sulphide) as the
most common pigment
to cause a reaction
large tattoos that he had obtained
over the years. Over a period of
several weeks he had visited the GP
with large ‘infected’ areas associated
with areas of the tattoo pigmented
with red dye. The GP had treated the
secondary infection and described
that, on post-infection examination, the
patient was left with raised, inflamed,
pruritic lesions, again located over
areas of red dye.
Figure 4. Case study. Left arm: raised areas, erythematous and scaling.
may accompany systemic autoimmune
disorders (McElvanney et al, 1994,
Mansour et al, 1991). This is relevant
to this case study as the patient had
a known history of acute bilateral
anterior uveitis three months prior
to the presenting tattoo allergy.
Histopathology reported sarcoid
granulomatous in the skin biopsies
taken from the affected tattoo areas.
Referral
A 35-year-old man was accepted by
General Practitioner (GP) referral
into a local, integrated dermatology
community clinic. The referral was
short and non-specific, giving little of
the patient’s background or longevity
of the tattoos. The referral described
the patient as a man who worked as
a domestic cleaner with a number of
Medical history
Listed in the medical history was a
known five-year history of epilepsy
and recent ocular hypertension. Also
listed was treatment for acute bilateral
anterior uveitis approximately three
months previous to this referral
and presentation of his symptoms.
Uveitis has known connections with
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Case HISTORY
Table 2
Specific Investigations.
Investigations in bold were carried out immediately
Skin biopsy
Electrolytes
Blood urea nitrogen
Creatinine
Serum calcium
Serum angiotensin-converting enzyme (ACE)
Liver function tests
Full blood count
24-hour urine calcium
Chest x-ray
Respiratory assessment (pulmonary function)
Electrocardiogram
sarcoidosis, which will be discussed
further in the case study. No
connection, mention or suspicion was
raised of cutaneous sarcoidosis in the
referral. Medications included Epilim
Chrono controlled release tablets
300mg bd and Sodium Valproate
bd 100mg. He was also using daily
Dexamethasone 0.1% eye drops for
his resolving uveitis. Relevant family
history listed only epilepsy. No known
allergies were reported other than
query red dye tattoo pigment at the
time of referral. He was a non-smoker,
drinking occasional alcohol and living
at home with his wife and three cats.
Consultation, history, examination
On meeting this patient for the
first time in clinic, he presented as
a very anxious gentleman with an
understandably anxious pregnant
wife. They had been told that he may
have an allergic reaction, but could
not understand the logic of this as
the tattoos had been obtained over
12 years ago. They had subsequently
searched the internet and had
concluded that he may have cancer
or another serious condition. On
the first GP visit, six weeks prior to
this appointment, the diagnosis was
thought to have been scabies due
to the intensity of the pruritus; he
had been treated with Derbac with
no effect. This was not mentioned
in the referral and had led to some
confusion with the patient. He was
Photographs and two
skin biopsies were taken
from the left arm with
the patient’s consent and
fast-track referral made to
secondary care for further
consultation and opinion.
subsequently treated for a secondary
skin infection with oral antibiotics. Once
the infection had subsided, the GP
considered a differential diagnosis of
a delayed allergic reaction connected
to the red tattoo pigment describing
raised pruritic lesions. At the time
of his clinical examination with the
specialist nurse, he presented with
well demarcated, raised areas outlining
both the peripheral edges and some
inner areas of the tattoo. Every red dye
area was affected to varying degrees,
involving arms, upper chest and back
(Figures 1-4). Although scaling and
erythema were seen, there was no
evidence of purulent or secondary
infection. He described all the affected
areas as being itchy and at times weepy
with developing crusts to some lesions.
Systemically he expressed tiredness
and a feeling of being ‘worn out’; he
was losing sleep due to the intense
itching, which was exaggerated at night.
As the assessing clinician I had not
seen a case like this before and,
following examination and history,
took consultation by telephone with a
senior registrar in dermatology at the
local acute department.
Diagnosis and investigations
The registrar’s advice was to obtain
4mm skin punch biopsies from the
affected areas for histopathology. If
there had been any weeping areas,
bacterial and viral swabs would have
been recommended. Biochemistry
would be required requesting the
following to confirm or exclude any
underlying systemic condition such as
sarcoidosis. The list indicates in bold
investigations carried out immediately;
the rest were instigated following the
histopathology report (Table 2).
Photographs and two skin biopsies
were taken from the left arm with
the patient’s consent and a fasttrack referral made to secondary
care for further consultation and
opinion. The photographs gave a
baseline of the current presenting
clinical picture and were to enable
further management advice from the
consultant dermatologist the following
day. He was commenced on topical
mometasone furoate once daily to the
affected areas with the plan to review
Table 3
Therapies for cutaneous sarcoidosis (adapted from IIayas et al, 2006).
First line
Second line
Third line
Topical corticosteroids
Intralesional corticosteroids
Oral corticosteroids
Chloroquine
Hydroxychloroquine
Methotrexate
Thalidomine
Allopurinol
Isotretinoin
Azathioprine
Chlorambucil
Quinacrine
Minocycline, doxycycline
Clofazimine
Etanercept
Fumaric acid esters
Topical Tacrolimus
Intralesional chloroquine
Excision
Laser
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Case HISTORY
in secondary care in 14 days with the
histology result. He was also given
aqueous cream with 1% menthol to use
as and when needed to relieve pruritus,
with dermol cream as a soap substitute
and moisturiser. He was already taking
an oral antihistamine purchased across
the counter. Reassurance was needed
as he was at the end of his tether and
confused by the potential diagnosis. All
investigations were explained to him
and his wife as a means to ascertaining
a definite diagnosis, although at this
time it was felt important to await
confirmation without adding more
anxiety and speculation. The main
priority was to relieve his symptoms
and anxiety and acquire appropriate
investigative results.
Histopathology —
further investigations
The histopathology report described
florid sarcoid granulomas in both
biopsies as a reaction to red granular
pigment. It was suggested that this was
either a local reaction or could reflect
systemic sarcoid. On his first secondary
care consultation, the patient was
informed of the potential sarcoidosis
diagnosis indicating that further tests
would be required to rule out a
systemic sarcoid. Further investigations
included a tertiary respiratory
assessment, including a chest X-ray.
All biochemistry results returned as
normal and the chest X-ray reported
no abnormalities seen. His respiratory
consultation ascertained no known
history of shortness of breath, cough,
chest tightness or wheeze, no chest
pain or haemoptysis. No loss of weight
or joint symptoms or evidence of
clubbing or lymphadenopathy. His chest
examination was unremarkable and his
pulmonary function tests indicated very
slightly reduced lung volumes.
The diagnostic outcome following
all investigations concluded that given
his uveitis history it was impossible
to completely rule out sarcoidosis at
this time. Observation was made that
a chest X-ray would have been useful
from his original symptom onset when
he presented to the GP, as any chest
changes may have resolved by the
time he reached secondary care. If this
36
was sarcoidosis it was now considered,
eight weeks later, that his condition
had spontaneously remitted. Follow-up
blood tests were recommended via
dermatology and skin care was to be
continued with nurse assessment. He
is now on a regular follow-up and his
current status is under review as the
skin lesions have failed to respond to
the topical corticosteroid. Although his
discomfort is now minimal, it is felt he
still requires monitoring. Consideration
is being given to a further excisional
biopsy and discussion is to be held in
a case review with opinions from
other consultant dermatologists
around the region.
In the United Kingdom, the
prevalence of sarcoidosis
in the adult population
is approximately 20 per
100,000 — worldwide the
incidence varies in every
country and race.
Sarcoidosis: incidence and
pathophysiology
To explain the investigation process
taken in this case more clearly and the
subsequent treatment, it is necessary to
give a brief overview of sarcoidosis as
a condition. In the United Kingdom, the
prevalence of sarcoidosis in the adult
population is approximately 20 per
100,000 — worldwide the incidence
varies in every country and race. The
true incidence is unknown, as some
people present with no symptoms
and spontaneously resolve. It seems
to be most prevalent among African
American women, followed by African
American men (Shetty et al, 2009).
Sarcoidosis is known as the ‘great
imitator’, a sometimes confusing clinical
picture with almost any morphology
ranging from lesions similar to
ichthyform, lichenoid, vasculitic,
psoriasiform, erythrodermic, verrucous,
papillomatous and ulcerative
(Tchernev, 2006). Once sarcoidosis
enters the differential diagnosis, the
clarification of the patient’s medical
history, onset and symptoms is
paramount and needs revisiting;
delay in diagnosis of sarcoidosis is
not uncommon (Judson et al, 2003).
Sarcoidosis is a fairly common
multisystem disease of unknown
aetiology producing noncaseating
epitheloid granulomas that can affect
any organ including lymph nodes, eyes,
ears, skin, liver, spleen, kidney, bone,
joints, nervous system and heart;
the lungs are the most frequently
involved organ hence the respiratory
assessment in this case (IIyas et al,
2006). A granuloma is a collection of
cells that normally help in removing
micro-organisms and antigens
from the body. If these granulomas
undergo necrosis (dead tissue) they
are called caseating, otherwise they
are noncaseating. The formation of
these granulomas is caused by an
exaggerated prolific immune response
to an unknown antigen at the target
organ. Antigens can vary and some
are more familiar than others such
as Mycobacterium tuberculosis,
Corynebacteria, Propionbacterium
acnes, herpes simplex virus, hepatitis C
virus, Epstein-Barr virus. Environmental
antigens are also reported, such as
some metals, pollen, clay, soil and
talc. Iannuzzi (2007) suggests that
sarcoidosis is a combination of
environmental and genetic factors.
Studies have not found a single
causative agent, although there is some
support for an inherited susceptibility.
Frequent observed immunologic
features include depression of
cutaneous delayed-type hypersensitivity
and a proliferation and activation of
T cells (TH1) at the site of disease.
The illness may be self-limited in
nearly two-thirds of patients, but
in 10-30% it is more chronic, with
recurrent episodes and remissions.
Sarcoid granulomas either resolve
and abate, or heal by fibrosis. It is the
fibrosis that can result in severe and
often irreversible organ damage and
dysfunction. Of those patients who die
with sarcoidosis, approximately 75%
do so due to severe lung involvement
leading to pulmonary fibrosis and
respiratory failure; others from
myocardial effects, mainly arrhythmias
and cardiac failure (Shorr et al, 2003).
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Case HISTORY
Treatment of cutaneous sarcoidosis
First-line treatment for cutaneous
sarcoidosis is aimed at suppressing the
formulation of granulomas. Treatment
with potent topical corticosteroids,
sometimes with occlusive dressings or
intralesional triamcinolone acetonide
is considered appropriate (IIyas et
al, 2006). If there is no response
or the involvement is extensive,
oral chloroquine is considered an
appropriate treatment, although relapse
after discontinuation is reported. The
initial dose is 250mg twice daily for 14
days, then 250mg daily for long-term
suppression (Zic et al, 1991).
If the patient remains symptomatic
and the chloroquine is considered
ineffective, oral prednisolone can be
used at a dose of 1mg/kg (max 60mg)
daily for up to 3 months and titrated
with monitoring of flares. A literature
review of subsequent second- and
third-line treatments produced a variety
of therapies with various randomised
controlled studies including patients
with multisystem disease, mostly for
pulmonary sarcoidosis. The range of
treatments have been listed for the
benefit of this case study as a reference;
it is acknowledged that second-and
third-line treatments have not been
discussed in depth in the context of this
case study (Table 3).
Patient outcome and conclusion
The patient in this case study is now
under review following investigations
and topical treatment therapy. The
pruritic symptoms have subsided,
although the raised areas in the red
dye pigment are still evident to a
lesser degree. On discussion with his
consultant we are now considering
oral chloroquine as a further first-line
treatment, together with a further
skin biopsy to examine the current
histopathology. He will also have
repeat blood tests and chest X-ray.
Reassurance has been given to the
patient that, to date, no evidence of
systemic sarcoidosis has been found,
making his prognosis favourable.
Learning points have come out of
this case study in the complexity of the
diagnosis of cutaneous sarcoidosis. As
38
a specialist nurse seeing new patients
from direct GP referral, a condition
such as cutaneous sarcoidosis needs
to be on the radar as a differential
diagnosis at an earlier stage in other
presenting cases. Not all nurse-led
community clinics have the benefit
of a dermatologist or clinician on site
and fast-track opinions should be
a mandatory logistic of these types
of clinic and primary care patient
pathways. Integrated dermatology
services lend themselves to this and
are consistent with clinical governance,
patient quality and the patient seeing
the most appropriate person for their
condition. The GP referral indicated
a possible allergic reaction with no
emphasis on suspicion of sarcoidosis
and was sent in via the primary care
pathway (Dermatology Workforce
Group, 2007). In hindsight, the referral
was more appropriate for secondary
care, although no ground was lost in
diagnosis because of the clinic’s level of
integration and experience.
The nature of this case study
presentation led us to the diagnostic
pathway quickly, but it could be
argued that it is not always a
considered differential in less obvious
manifestations and morphology. From
a dermatology nurse aspect and
professional development point of view,
a more comprehensive knowledge
of this condition, relevant history
and cutaneous presentation was
felt relevant. Apart from sarcoidosis,
tattooed skin can present with other
cutaneous conditions relevant to
dermatology referrals. Taking into
account the popularity of tattooing
in Western society, education both
in primary and secondary care,
particularly at nurse-led services level,
would seem appropriate. DN
Gilbert GS (2001) Tattoo History: a
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