Volkmer

UV and Children‘s Skin
Beate Volkmer and Rüdiger Greinert

Division of Molecular Cellbiology
Center of Dermatology, Elbeklinikum Buxtehude
Germany

Non-Ionizing Radiation & Children‘s Health
International Joint Workshop 18 – 20 May 2011, Ljubljana, Slovenia

Epidemiological studies indicate that sunburns in
childhood are associated with an enhanced risk of
malignant melanoma later in life
e.g. Oliveria SA, Saraiya M, Geller AC, Heneghan MK, Jorgensen C. Sun exposure and risk of
melanoma. Arch Dis Child. 2006 Feb;91(2):131-8

Migration studies indicate that prepubertal high UV-
exposure is associated with an enhanced risk of
malignant melanoma and BCC later in life
e.g. Kricker A, Armstrong BK, English DR, Heenan PJ. Pigmentary and cutaneous risk factors for
non-melanocytic skin cancer--a case-control study. Int J Cancer. 1991 Jul 9;48(5):650-62


UV-Exposure and number of Nevi in Childhood
(The Hamburg School Children Study, n= 13,500)

Number of Holidays in the South (<48°)

Number of severe 0 1 2 3 4 5+
sunburns
0 9,79 11,11 11,70 12,84 13,53 16,95

1 11,12 11,92 14,24 13,67 12,80 13,80

2+ 11,39 12,70 12,68 19,57 30,48 20,21

Dulon M, Weichenthal M, Blettner M, Breitbart M, Hetzer M, Greinert R, Baumgardt-Elms C, Breitbart EW. Sun exposure and number
of nevi in 5- to 6-year-old European children. J Clin Epidemiol. 2002 Nov;55(11):1075-81


UV-Exposure and number of Nevi in Childhood
(The Hamburg School Children Study, Follow up)
Frequency distribution of nevus cell nevi

Age 5-6 years
Age 9-10 years

Number of nevus cell nevi


Animal study: In contrast to adult mice neonatal mice
do not show an immune-response after UVB-radiation.
This might reduce the possibility to recognize and
remove damaged cells.
Wolnicka-Glubisz A, Damsker J, Constant S, Corn S, De Fabo E, Noonan F. Deficient inflammatory
response to UV radiation in neonatal mice. J Leukoc Biol. 2007 Jun;81(6):1352-61


Is there any difference between
children‘s skin and adult skin?

•There is no difference in sunburn sensitivity MED*

•There is a difference in thickness due to stucture of
the rete ridges

•There is a difference in contribution of vellus,
intermediate and terminal hair type
*Cox NH, Diffey BL, Farr PM. The relationship between chronological age and the erythemal
response to ultraviolet B radiation. Br J Dermatol. 1992 Apr;126(4):315-9


Sunbed use and melanoma risk

Start of use of sunbeds
Before the age of 35
Increase risk of melanoma
Later in life by

75 %

IARC,Int. J. Cancer, 2006

Some numbers from Germany
2008
SUN study (Sunbed-Use: Needs for Action-Study 2008)
Diehl et al., Int. J. Public Health (2010)
Schneider et al. Acta Derm. Venerol. (2009)
Börner, F. et al. Gesundheitswesen, (2009)

User prevalence* time
(18-45 years)
46.7 % ever
Average current user (last 12 month)
Extrapolation % whole Germany: 14 Mio of about 30 Mio of 18-4515 visits/year ever
21.0 for Last 12 month reported a mean of years old have
been exposed to sunbed UV. About 3 Mio started (first time)  18 years of age !
(1, 120).
18.4 % Last 6 month Exposer time (mean): 13.6 min  4.3
17.4 % Last 3 month
12.5 % Last month (1-10
times)
* City of Mannheim (327.000 Inh.), southern Germany, according to telefon
interviews

Some numbers from UK
Thompson C.S. et al. , BMJ (2010): Sunbed use in children aged 11-17 in England: face to face quota
sampling surveys in National Prevalence Study and Six Cit Study

• Already 6% of those aged 11-17 had used
a sunbed (8% in girls, 3.5 % in boys)
• Sunbed use gradient from „north“ to
„south“
(11% vs 4.2 %)
• In six cities Liverpool and Sunderland
(20% and 15.6 %) showed the highest use
(with rates especially high in girls (15-17
years or from lower social grades
• 23 % of children used a sunbed at home

Different structure of the rete ridges

Adult skin Children‘s skin

Basal layer containg epidermal stem cells and melanocytes


Consequences?
 The basal layer of the epidermis is more
exposed to UV-irradiation on the base of
the rete ridges in children‘s skin as
compared to adult skin.

 Interfollicular epidermal stem cells as well
as melanocytes are located in the basal
layer of the epidermis

 Epidermal stem cells are supposed to be the
most important target for the carcinogenic
effect of UV-irradiation related to non-
melanocytic skin cancer


UV-induced specific DNA lesions

Trends in Molecular
Medicine, 5, 86-94,
1998

acute chronic

Ko A1
C1

Proband 3_03
Skin type I-II
IMED = 350 J/m²
A2 C2

After 6 weeks

Cyclobutane-Pyrimidine-Dimer retaining basal cells
(CRBC) are induced by UV-irradiation

6 week after irradiation human skin
in-vivo with SSR, 1.5 MED

Putative epidermal
stem cells


About 80% of CRBCs are melanocytes

Epidermis Epidermis Epidermis

4 4 4

3 3
3
1 1 2 1 2
2
Dermis
Dermis a b Dermis c

Skin section with CRBCs: a) melanocyte-marker (Melan-A)(red);nuclei are
labelled with Dapi, b) anti-CPD-antibody (green) c) merge of a) and b). (1) and
(4): melanocytic CRBC, (2) undamaged melanocyte, (3) non-melanocytic
CRBC

About 20% of CRBCs are keratinocytes

Epidermis Epidermis Epidermis

Dermis Dermis b Dermis c
a

Skin section with CRBCs stained with a) an anti-cytokeratin-antibody (red), b)
an anti-CPD-antibody (green) c) merge of a) and b).


Consequences?
 The special structure of the rete ridges in
children‘s skin can lead to enhanced
induction of melanocytic and keratinocytic
CRBC at the base of the rete ridges

 Due to the special structure of the rete
ridges in children‘s skin melanocytic
precurser cells that are supposed to be
located in the dermis* are at higher risk to
be exposed to UV-radiation
*Li L, Fukunaga-Kalabis M, Yu H, Xu X, Kong J, Lee JT, Herlyn M. Human dermal stem cells
differentiate into functional epidermal melanocytes. J Cell Sci. 2010 Mar 15;123(Pt 6):853-60


Difference in contribution of vellus,
intermediate and terminal hair type

 At birth all hair follicles are present, no further follicles
will develop throughout life

 Prepubertal children have a much higher proportion
of vellus hair compared to adults

 During puberty in some areas of the body vellus hair
develop into terminal hair with follicles relocated
deeper within the skin
Garcia, A.M.G. et al.: Melanoma:is hair the root of the problem? Pigment Cell Melanoma Res., 24, 110-118 (2011)

Consequences?

Stem cell niche: multipotential
stemc ells e.g for keratinocytes,
neurons, glia, smooth muscle cells,
and melanocytes


UV radiation

Blistering sunburn

Epidermis  UV damaged stem cell

Bulge region
362 m from surface of skin

Stem cell
Vellus hair shaft
Bulge region
1191 m from surface of skin
Stem cell

Terminal hair shaft

A positive correlation between number of vellus hair follicles
and melanoma incidence is described by Garcia et al.


Conclusion
There is no difference in UV-sensitivity between children‘s
and adult skin in relation to sunburn

Structural differences can lead to higher UV-exposure of
epidermal stem cells and melanocytic precursor cells,
potentially enhancing the skin cancer risk in later life

In children vellus hair is the primary hair type with a probable
higher UV-exposure of multipotenial stem cells in the bulge
region of the hair follicle

Since during puberty the vellus hair develop into terminal
hair with follicles located deeper and thus more protected in
the skin these data for the first time can explain the data of
migration studies.

Future aspects
Comprehensive data related to the UV-sensitivity of children‘s
skin are still lacking

In vitro models for children‘s skin have to be developed to get
more basal data like e.g. DNA-repair capacity

The involvement of interfollicular and follicular epidermal stem
cells as well dermal stem cells in the development of malignant
melanoma and non-melanocytic skin cancer has to be
investigated


Thank you


Volkmer

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