ARTICLE
Photoaging is the term used to describe the clinical and histological
findings in chronically sun-exposed skin. Kligman first described the
hallmark histological signs of chronically sun damaged skin viz, accumulation
of disorganized, coarse bundles of fibers which stained for elastic tissue
and termed this elastosis. In the 30 years since that landmark observation,
a wide variety of clinical and histological changes have come to be associated
with chronic ultraviolet damage to skin. The clinical consequences are
responsible for the majority of undesired clinical features associated
with aging and so called "premature aging of skin". Until relatively recently,
it was believed that most of these changes were the result of UVB damage
and that UVA was relatively "safe". There now is commanding evidence to
implicate UVA as a major pathophysiological factor in photoaging.
Clinical-histological features
Table I summarizes the major clinical-histological
features of photodamaged skin.
Stratum corneum
A prominent feature of photodamaged skin is a pronounced thickening
of the stratum corneum. This thickening is the result of faulty degradation
of stratum corneum desmosomes. As the stratum corneum thickens, the outer
layers become somewhat dehydrated. As a result, the outer stratum corneum
becomes stiffer and micro Þssures develop. Micro Þssuring
leads to clumps of stratum corneum cells partially tearing away. These
clumps of uplifted cells are visible as flaking and feel rough to the
touch. Many years ago, we inspected the skin of large numbers of individuals
ranging from teenagers to those over ninety. It is apparent, even in teenagers,
that the sun exposed arms and lower legs are rougher and often show flaking
and are clearly different than sun protected skin such as the upper inner
forearm near the axilla.
Epidermis-keratinocytes
Sun exposed skin typically shows a thickened epidermis. This increase
in the viable epidermal compartment indicates a hyperproliferative state,
possibly indicating a chronic wound like condition and a chronic attempt
at repair. Epidermal DNA damage can be seen in the form of dysplasia,
basal and squamous cell carcinoma. Another histological hallmark of photodamage
are so called "sun burn" cells. These cells show pyknotic nuclei and a
necrotic, eosinophilic cytoplasm. These cells are now referred to as apoptotic
cells i.e., cells engaged in a programmed cell death or suicide
presumably because sufficient DNA damage has occurred. In a more subtle
fashion, DNA damage can be seen by use of a monoclonal antibody to the
p53 enzyme system - the so called guardian of the genome. When epidermal
DNA is damaged this system is activated to initiate repair. Defects in
this system in the form of mutations leads to an increased risk for cancer.
In addition to precancerous dysplasia and cancer, benign hyperproliferative
lesions such as seborrhoic keratosis can develop.
Recently, we have come to realize that epidermal inclusion cysts (milia)
may also be a sign of chronic ultraviolet damage. The index case was a
45 year old male with basal cell nevus syndrome who had hundreds of milia
on his face, without any history of dermabrasion or other resurfacing
procedures. We examined more than 500 women who had previously been involved
in clinical trials for photodamage and found a high correlation between
their photodamage grade and the presence and number of milia. In that
group, there were three women who had numerous milia with mild photodamage.
These women had siblings and/or parents who also had large numbers of
milia suggesting a possible genetic factor. Follicular epithelial retention
hyperkeratosis and comedone formation is another well recognized feature
of chronic photodamage.
Epidermis-melanocytes
Increased numbers of melanocytes and melanocytic hyperplasia resulting
in solar lentigos, "age spots" and sun burn freckles are well recognized
consequences of chronic ultraviolet damage. The role of ultraviolet light
in melanoma remains unsettled in terms of which wave lengths are involved
and how central to melanoma development UV is but none doubt its importance.
Dermis-matrix
A histological hallmark of photoaging is a replacement of the normal
dermal matrix of collagen, elastin and glycosaminoglycans by large bundles
of coarse elastic fibers and decreased collagen. The clinical consequence
of "elastosis" is pronounced wrinkling and in advanced cases, yellowish
cobblestone appearance associated with pronounced sagging. This process
is often accompanied by a brisk neutophilic infiltrate which often can
be appreciated clinically and is referred to as heliodermatitis or dermatoheliosis.
Neutrophil elastases may play a prominent role in damage to elastin and
the subsequent wrinkling or sagging. The role of UV in the degeneration
of surrounding collagen is now more fully understood and is the consequence
of ultraviolet light increasing the activity of metalloproteinases. This
family of 14 different proteinases can act on a broad range of substrates
and can be activated in vivo by a single exposure to UV. The mechanism(s)
of elastosis remain unclear. The major consequence of these changes in
the dermal matrix is wrinkling. Wrinkles don't have a histological marker
but rather can be best thought of as stress fractures from material which
has aged. The radiating quality of wrinkles is similar to that seen in
materials such as buildings and bridges. With more pronounced changes,
skin "settles", which is seen clinically as sagging.
Dermis-vasculature
Two changes can occur. Some patients show loss of the papillary plexus,
flattening of the rete ridges and loss of the papillary dermis. Clinically,
these individuals have a sallow washed out appearance. The other finding
is that of a proliferative response producing dilated, enlarged vessels
in the papillary and mid-dermis. Clinically, these are seen as telangiectasis.
Dermis-sebaceous gland
Sebaceous gland enlargement is another feature of chronic ultraviolet
damage. Clinically, this can be seen as small, yellowish nodules or in
more advanced cases as a thick, coarsening of the skin with large, dilated
follicular openings from which sebaceous material can be squeezed out.
Vulnerable phenotypes
It has been known for many years that fair skinned individuals, particularly
those of Celtic ancestry, are particularly vulnerable to the acute adverse
effects of ultraviolet light i.e., sun burn. More recently, we
have come to realize that there is a phenotype which appears to be more
vulnerable to the chronic adverse effects of UV. These individuals have
red hair, blue eyes and have a Celtic background but have the ability
to tan often fairly deeply, after suffering initial burning. Typically,
they have a very fair Celtic parent who burns and tans little or none
while the other parent tans easily and rarely burns. The vulnerable offspring
is able to sustain more exposure because their tan prevents burning. Usually,
these individuals are infrequent users of high SPF sunscreens and pride
themselves on their ability to tan while family members can't. These individuals
develop dry skin, a leathery wrinkling and pigmentary changes at a relatively
early age (late 20s to early 30s) and by their mid-forties they tend to
look older and are extremely unhappy.
Role of UVB and UV
In order to minimize photodamage, we must first understand which wave
lengths are responsible for which changes and then use sunscreens with
appropriate filters in combination with sensible lifestyle exposure patterns
and use of clothing, hats, umbrellas, etc.
Ultraviolet light is artificially divided into very short wave UVC (none
reach our planet), UVB (290 to 320 nanometers) and UVA which is subdivided
into UVA II (320 to 340) and UVA I (340 to 400). UVA makes up approximately
95% of the ultraviolet to which we are exposed.
Up until relatively recently, the main focus of research interest was
UVB particularly in terms of non-melanoma carcinogenesis. UVB is far more
energetic than UVA and clearly is the primary event in squamous cell cancer
and plays an important role in basal cell cancer development.
Table II contains a list of other findings in
humans or experimental animals. Besides non-melanoma cancer, the other
major area of focus was the effect of UVB on epidermal Langerhans cells
and consequent immune suppression.
In recent years, in vivo studies in human volunteers have demonstrated
that repetitive low doses of UVA II and I (comparable to that obtained
during every day activities) can have profound effects on all types of
skin. These studies indicate the need for much more effective broad protection
against both UVA II and I. Of particular importance are the findings which
show a possible link between UVA and malignant melanoma.
In a series of studies, Lavker and Kaidbey have shown that repetitive
low dose UVA plays a central role in stratum corneum hyperkeratosis (dry
skin), epidermal DNA damage (apoptosis, p53 expression), proliferation
of the epidermis, Iysozyme deposition in elastic fibers (elastin damage)
and heliodermatitis.
Furthermore, other findings of photodamage in checking stratum corneum
thickness, viable epidermal thickness, apoptoses and Langerhans' cell
depletion were found. In addition to UVA and UVB exposure, these individuals
had 1/2 an MED exposure through a typical SPF 22 (UVB filtration and some
UVA) which clearly was not protective.
These studies, coupled with more recent preliminary studies on the effects
of UVA on dermal blood vessels and sebaceous glands demonstrate that UVA
is far more damaging than previously suspected. Moreover, long wave UVA
I also is clearly harmful particularly for the deeper dermal changes associated
with wrinkling and probably telangiectasis and sebaceous gland hypertrophy.
Once these findings were made, the clinical consequences were obvious
and a better understanding of many patients was possible.
Of particular relevance was the ability to understand why many patients
who were religious users of SPF-15 to 30 sunscreens still developed pronounced
wrinkling.
A 67 year old retired school teacher avoided the sun all her life and
rarely drove more than 3 or 4 miles a day. The left cheek shows extensive
elastosis and sagging while her right cheek shows none. For nearly 40
years she stood in front of large windows and was exposed to 4 to 5 hrs
a day of bright sun light. Her major exposure was UVA to one cheek through
window glass.
The implications of these studies are clear. We must use strategies
to better protect ourselves against not only UVB but also broad spectrum
UVA. Lifestyle decisions and wearing protective clothing is part of the
overall strategy. The use of broad spectrum UVB and UVA sunscreens is
clearly desirable.
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