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Exposure of the skin to UV light has acute, short-term effects and chronic, long-term effects, both of which are wavelength-dependent. Profound effects also occur with non-erythemogenic doses of UV light
UV light affects the skin's immune system, exerting both pro- and anti-inflammatory responses
UV light induces several different types of DNA damage in a wavelength-dependent manner, such as pyrimidine dimers (UVB ≫ UVA) and oxidative guanine base modifications (primarily UVA); pyrimidine dimers are the most important pre-mutagenic DNA lesions
Several DNA repair pathways are involved in the processing of UV light-induced DNA damage, including nucleotide excision repair, base excision repair, translesional DNA synthesis, and recombination repair
UV light-induced mutations, which play a pivotal role in photocarcinogenesis, are different from those induced by other mutagens. Some base substitution mutations (e.g. C→T, CC→TT) are so typical for UV light that they have been termed “signature mutations”
Disorders with an increased frequency of UV-induced skin cancers are characterized by an impaired cellular or host response to the effects of UV light
Dermatologists are confronted daily with the effects of UV light on the skin, and often deal with them in a seemingly contradictory way. On the one hand, they have the responsibility of warning their patients against the deleterious effects of sunlight, such as sunburn, photoaging and sun-induced skin cancers, and on the other hand, they use UV irradiation to treat skin disease. As with all medical interventions, dermatologists are weighing the risks versus the benefits when they use UV light for therapeutic purposes. In the phototherapy of inflammatory skin diseases, dermatologists also try to avoid the proinflammatory properties of UV irradiation (e.g. the capability to induce sunburn) by choosing suberythemogenic doses (see Ch. 134 ). This clearly indicates that doses of UV light that do not induce sunburn still have profound effects on the skin. This applies not only to its short-term effects, but also to its long-term effects. A third and important aspect of photodermatology is the diagnosis and treatment of photosensitive or photoaggravated skin disorders (see Ch. 87 ).
The sun emits UV radiation as part of an electromagnetic spectrum (see Fig. 134.1 ). It is usually subdivided, rather arbitrarily, into UVC (200–290 nm), UVB (290–315 nm), and UVA (315–400 nm). UVA has been further subdivided into UVA1 (340–400 nm) and UVA2 (315–340 nm). Of note, some authors use 320 nm as the demarcation between UVA and UVB. More than 95% of the sun's UV radiation that reaches the earth's surface is UVA. Practically all of the UVC, and much of the UVB, are absorbed by the oxygen and ozone in the earth's atmosphere, so that UV radiation below 290 nm is virtually undetectable at ground level. Nevertheless, the remaining UV radiation can still be absorbed by biologic molecules (DNA, protein, lipids), and it can damage and kill cells.
To survive in our environment, all living organisms had to develop protective mechanisms in order to prevent UV-induced killing and to maintain the stability of their genome. Such defenses include the development of UV-absorbing surface layers, enzymatic and non-enzymatic anti-oxidative defenses, repair processes, and removal of damaged cells. Through evolution, humans have lost most of the UV-protective fur, which remains an effective UV-protector only on the scalp. Nonetheless, the human skin is quite effective in protecting the rest of the organism from the harmful effects of solar UV irradiation, since UV radiation does not penetrate any deeper than the skin. Within the skin, the depth of penetration of UV light is wavelength-dependent – i.e. the longer the wavelength, the deeper the penetration ( Fig. 86.1 ). While UVA readily reaches the dermis, including its deeper portions, most of the UVB is absorbed in the epidermis, and only a small proportion reaches the upper dermis. UVC, if it reached the earth's surface, would be absorbed or reflected predominantly by the stratum corneum and the upper layers of the epidermis.
However, when thinking about the biologic effects of different wavelengths in the different layers of the skin, it is necessary to consider that a particular wavelength can even have a biologic effect in a layer that it does not reach. For example, secretion of a proinflammatory mediator in the epidermis can produce subsequent signaling in the dermis and possibly even the subcutaneous fat .
Some of the UV light reaching the skin is absorbed by biomolecules. A light-absorbing molecule is called a chromophore. Upon absorption of the radiation's energy, this chromophore is elevated to an excited state. Ensuing photochemical reactions may either change the chromophore directly, or, through energy transfer in a so-called photosensitized reaction, indirectly change a molecule other than the chromophore. Absorption is wavelength-dependent and if a photon (depending upon its wavelength) is not absorbed, a photochemical reaction cannot ensue. For UVB, the most important chromophore is DNA while a typical UVA- and visible light-absorbing chromophore is porphyrin.
Knowledge of absorption spectra of molecules is critical for understanding photobiologic consequences of UV absorption, including photomutagenesis of DNA by UVB, the efficacy of UV filters in sunscreens, and the elicitation of photodermatoses by certain wavelengths of UV light. An absorption spectrum defines the probability that a molecule will be excited by a certain wavelength. While the absorption maximum predicts the wavelength at which absorption is most likely, other wavelengths can still be absorbed. For example, the absorption maximum of DNA is 260 nm, which is within the UVC range. However, UVB still effectively excites DNA, and even UVA and visible light can do so. This explains why DNA photoproducts, a type of DNA damage induced by a photochemical reaction following direct excitation of the DNA molecule, are not only induced by UVB, but also by UVA, and even by visible light, albeit at a much lower efficacy.
Both short- and long-term effects of exposure to UV light are wavelength-dependent. However, when comparing the photobiologic properties of UVB with those of UVA, it is important to remember that they are not two different entities, but rather a continuum of wavelengths, with gradually changing properties, and that the division between UVA and UVB is rather arbitrary.
Visible, short-term, cutaneous effects of UV irradiation include sunburn (solar erythema and possibly blister formation, followed by desquamation) and tanning. Microscopically, short-term effects include epidermal edema with spongiosis, formation of sunburn cells (apoptotic keratinocytes), acanthosis, hyperkeratosis, depletion of Langerhans cells, and an increase in basal layer and suprabasal melanin content, in addition to inflammatory infiltrates of lymphocytes and neutrophils and vasodilation. On a cellular and molecular level, UV exposure induces a multitude of damage responses, including the induction of stress proteins, repair processes, and cytokine production (e.g. IL-1, IL-6, TNF). In a dose-dependent manner, exposed cells can either undergo apoptosis (visible histologically as sunburn cells) or cease proliferating (cell cycle arrest) in order to undergo repair. Hyperproliferation may follow the initial growth arrest, visible histologically as epidermal thickening. The inflammatory response in the sunburn reaction is likely due to an activation of innate immunity . Lastly, UVB-induced activation of transient receptor potential ion channels in keratinocytes with subsequent calcium influx has been shown to mediate sunburn pain .
The ability to induce sunburn ( Fig. 86.2 ) rapidly declines with increasing wavelength. For example, UV light with a wavelength of 360 nm is approximately 1000-fold less erythemogenic than light with a wavelength of 300 nm. A UVB-induced sunburn reaches its peak between 6 and 24 hours after exposure. An immediate erythema reaction is rarely observed. In contrast, after exposure to a very high dose of UVA, an immediate erythema reaction can occur, followed by a distinct delayed erythema after 6 to 24 hours. However, unless patients have increased UV sensitivity (e.g. decreased minimal erythema dose [MED] to UVA; see Ch. 134 ), the doses of UVA present in natural sunlight are not sufficient to induce a sunburn. DNA is thought to be the chromophore for the delayed erythema reaction associated with UVB .
The tanning response of human skin to sun exposure is biphasic and also wavelength-dependent. Immediate pigment darkening occurs during and immediately after exposure, and is due to alteration (e.g. oxidation) and redistribution of existing melanin. It is most prominent with UVA. Delayed tanning is usually the result of an exposure to UVB, and it peaks approximately 3 days after sun exposure. Fair skin (skin type II) usually tans only with UVB doses above the erythema threshold, i.e. only with prior sunburn. Darker skin (skin types III and higher) also has a significant tanning response to suberythemogenic doses, i.e. without a prior sunburn. A UVB-induced tan is characterized by an increased number of melanocytes, increased melanin synthesis, increased arborization of melanocytes, and increased transfer of melanosomes to keratinocytes (see Ch. 65 ). A UVA-induced tan, such as from the use of a tanning bed ( Fig. 86.3A ), provides 5–10 times less protection against a sunburn from subsequent UV exposure than a UVB-induced tan, probably because a UVA-induced tan is characterized by less pronounced epidermal thickening and hyperkeratosis.
An individual's tendency to develop sunburn and tanning after sun exposure has been used to categorize skin phototypes (see Table 134.3 ). These categories of an individual's susceptibility to short-term effects also correlate with the individual's susceptibility to long-term effects following sunlight exposure. In general, those individuals with higher acute sun sensitivity are also at greater risk for developing skin cancer after chronic UV exposure.
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