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Commentary Vitiligo, sun and skin cancer
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More
on the subject vitiligo, sun and skin cancer A
commentary by Professor KU Schallreuter MD PhD Clinical
Director of the Institute for Pigmentary Disorders in association with E.M.
Arndt Universiy of Greifswald/Germany and University of Bradford/UK This
is a response to the special feature article in Dispatches 40 / October
2005 of the UK Vitiligo Society and to a recent article in “The Times”
T2 Body and Soul section about the skin cancer risk in patients suffering
from vitiligo. What
is vitiligo? This
seems a redundant question. However,
it seems important to recognise that vitiligo
is a disease according to the World Health Organisation. Vitiligo
is neither a condition nor a symptom. The
characteristics of this disease are the acquired sudden loss of the
inherited skin colour. Despite its long recognition, the cause of this
disease is still unknown. The
loss of the skin colour yields white patches of various sizes which can be
localised anywhere on the body. The disease affects all races, men and
women and all age groups. Approximately 1 in 200 of the world population
develops vitiligo. The
affected individual shows often severe disfigurement, particularly when
the face and the hands are involved. However,
not all white skin patches are vitiligo. There are other conditions and
diseases which are associated with white skin. A long time ago the term
leucoderma has been introduced. This word originates from the Greek
language and means white skin. Clearly it seems mandatory to make the
correct diagnose. This can be done by Wood’s light. Vitiligo shows a
very characteristic fluorescence under this condition which is absent in
other leucodermas (Schallreuter
et al, Science (1994)) Sutton
Nevus (Halo-Nevus) is not vitiligo Leukodermas
of other origin are for example the Sutton Nevus also called Halo-Nevus.
Despite both vitiligo and Sutton nevus can occur together at the skin of
the same individual, it has been shown that these are two very different
diseases (Schallreuter
KU et al Arch Dermatol Res (2004)) Future
work needs to show why both vitiligo and Halo-Nevi frequently occur
together. Skin
colour and sun protection For
decades it was believed that skin colour with its pigment (melanin)
content fosters sun protection. However, the sun protection factor (SPF)
is only between 2-3 for the brown / black melanin (eumelanin), while the
red pheomelanin hardly protects at all, it is even photoactive and
generates reactive oxygen species (ROS) (Chedeckel
MR and Zeise L, Lipids (1998, Johnson BE et al Nat New Biol (1972)).
It is becoming evident that besides melanin formation many other
mechanisms and factors are in place to defend the human body against
environmental reactive oxygen species (ROS) formation (Schallreuter
KU and Wood JM Photobiology (2001)). ROS can also be generated by
ultraviolet light directly inducing a plethora of signalling and defence
mechanisms. In
vitiligo patches the pigment is mostly completely absent, but not all
individuals suffer from sun burn despite sun exposure (Schallreuter
KU et al, Dermatology (2002)). Moreover,
it has been documented at least in 2 major studies that vitiligo per
se does not necessarily coincide with increased sun sensitivity (Calanchini-Postizzi
E and Frenk E Dermatologica ( 1987); Schallreuter KU et al (2002)) Skin
ageing and vitiligo Interestingly,
the skin of vitiligo sufferers does not age with the same speed compared
to age and sex matched healthy people who do not have vitiligo (Schallreuter
KU et al (2002)). The results stem from a clinical study of patients
with vitiligo who did not avoid sun exposure completely. Hence, it would
be of great value to understand this phenomenon. This observation clearly
indicates that some other protective mechanisms must be in place to yield
this result. However,
it is also beyond any doubt that excessive sun exposure over time can
induce non melanoma skin cancer (NMSC) in general in susceptible
individuals. The
development depends on the genetic background and on the accumulation of
sun exposure times / sunburns over time. In
this context it is noteworthy that fair skin people who always burn and
never tan are much more prone to develop skin cancer compared to good
tanners and dark skin coloured individuals. But there are also exceptions.
Even dark skin people can occasionally be very sun sensitive. Vitiligo
and skin cancer The
result of two major studies showed that patients with vitiligo do not have
a higher risk to develop sun induced skin cancer (Calanchini-Postizzi
E and Frenk E (1987) , Schallreuter KU et al (2002)). In
the recent past an issue was put forward that PUVA therapy which is a
frequently used treatment modality for vitiligo could be of potential risk
to enhance the risk of skin cancer and their precursors (actinic keratosis)
in these patients (Halder
RM et al Arch Dermatol(1995)). Considering the amount of rays which
these individuals receive, it seemed reasonable to question the possible
side effects. However, until now there is no documentation in the
literature about a true coincidence. (Westerhof
W and Schallreuter KU Clin Exp Dermatol (1997)). A recent publication
by Grimes states that there is also no enhanced risk after the use of
narrowband UVB exposure which is a treatment modality utilised as mono
therapy with increasing doses 2-3x per week in adults and even in children
(Grimes
P, JAMA ( 2005)). Vitiligo
and melanoma Malignant
Melanoma (MM) is another skin cancer which can be very dangerous if not
recognised early. There are many reports linking this malignancy with
altitudes and excessive periodic sun exposure.
People
with very fair skin (those who never tan or only very slightly) do have a
higher risk to develop melanoma compared to dark skin people at any body
site regardless of sun exposure or not. These tumours can develop in
existing moles but they can also arise totally new as pigmented as well as
non-pigmented tumours. Early recognition and excision are important for
the outcome. The
observation that melanoma is more frequent in patients with vitiligo
originates from a study which included 623 Caucasian patients with
melanoma of the Oncology Clinic at the Department of Dermatology at the
University of Hamburg/Germany (Schallreuter
KU et al, Dermatologica (1991)). In
this study 11/623 patients with melanoma had a true vitiligo long before
their melanoma was diagnosed. Considering that 1 in 200 has vitiligo and 1
in 12,000 develops melanoma, these results suggested a significantly
higher risk to develop melanoma for patients with vitiligo and fair skin (Schallreuter
KU et al, Dermatologica (1991)). In
our Institute for Pigmentary Disorders we have indeed found in 2 Caucasian
patients with vitiligo melanoma in a patient group of 1800 Caucasian
patients with vitiligo supporting the above findings (Schallreuter
KU, unpublished results). Based
on the above results the take home message and recommendation is that
patients who have vitiligo should undergo an annual total body examination
at their Dermatologists in order to recognise a possible melanoma as early
as possible. Melanoma
associated leucoderma Some
individuals with melanoma develop patches of white skin in the vicinity of
their melanoma or after their tumour had been excised.
In this context it seems important that these white patches are not
vitiligo. This skin shows a very different molecular biology and
biochemistry compared to true vitiligo (Kothari,
S PhD Thesis U of Bradford 2005). Therefore the term melanoma
associated leucoderma seems more appropriate as already suggested earlier
by the late Fitzpatrick. Are
white skin patches associated with melanoma beneficial for the outcome ? The
development of white patches anywhere on the skin in association with
melanoma was interpreted to be a beneficial sign in the outcome for
survival time. There is still an ongoing debate whether the development of
such leucoderma associated with melanoma is of true value for the
individual’s outcome or not (Lerner
AB, Nordlund JJ Arch Dermatol (1977); Nordlund JJ, Lerner AB Arch Dermatol
(1979); Nordlund JJ et al J Am Acad Dermatol (1983)). This author
feels that there is at the present time not enough evidence to support
this statement. Larger patient groups are needed in order to conclude.
Therefore, it is simply not correct to advise patients with vitiligo that
they have a decreased risk to develop melanoma and that they are well
protected against this tumour.
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