Marked morphologic changes in all parts of the skin, except perhaps the subcutaneous tissue, are recognized as consequences of exposure to UVR. These changes underlie the clinically observed sagging, wrinkling, leathery texture, and blotchy discoloration of skin typically associated with actinic damage.
Marked morphologic changes in all parts of the skin, except perhaps the subcutaneous tissue, are recognized as consequences of exposure to UVR.
These changes underlie the clinically observed sagging, wrinkling, leathery texture, and blotchy discoloration of skin typically associated with actinic damage. It is unclear how much exposure and how much time is required to effect these changes, although it is evident that clinically normal appearing skin can show pathologic signs of sun damage upon histologic and ultrastructural examination. It is known that individuals with fair complexions are more susceptible to this damage.
In the epidermis UVR-induced changes include aberrant tissue architecture and alterations in keratinocytes and melanocytes and functional changes in Langerhans cells.
Sun-exposed epidermis becomes thickened as much as twofold compared to sun-protected skin and is disorganized, showing evidence of hyperkeratosis, parakeratosis, and acanthosis.
Keratinocytes lose their typical alignment and progressive flattening, show inclusions in the nucleus, and accumulate excessive amounts of melanosome complexes above the nucleus (capping). At the ultrastructural level, clumped keratin filaments and alterations in electron density of some basal cells are characteristic.
Keratinocytes of the more differentiated epidermal layers (upper spinous, granular, and cornified) show few, if any, cytologic changes.
In spite of evidence for morphologic change, there are no data indicating altered keratinocyte differentiation as a result of sun exposure. Furthermore, it is not known how UVR interactions with light-absorbing molecules within the keratinocytes (e.g., DNA, keratins, lipids) correlate with the changes in morphology.
Two other cells of the epidermis are also affected by UVR. The melanocyte, with its melanin pigment-containing melanosomes, is the primary cell involved in photoprotection of the skin. In sun-damaged epidermis, these cells enlarge, increase in number, and migrate to higher levels of the epidermis. UVR also affects Langerhans cells in both animal and human skin by altering their immunologic function. Even low doses of UVB can reduce their antigen-presenting capability, block the normal effector pathway, and evoke an inappropriate response by activating T suppressor networks. It is unclear whether UVR affects Langerhans cells both directly and indirectly through soluble factors released by damaged keratinocytes.
The dermal-epidermal junction loses its rete ridges forming a flattened interface between the epidermis and dermis. This kind of abutment is more susceptible to shearing forces than the normal interlocked system of epidermal rete ridges and dermal papillae. At the ultrastructural level, regions of reduplicated lamina densa are evident. This change is not unique to photodamage but is characteristic of trauma to the epidermis by wounding and/or by disease.
UVR causes unique dermal damage such as alterations in architecture, matrix composition, vascular structure and function, and cellular activities. The connective tissue immediately beneath the epidermis (Grenz Zone) contains large bundles of densely packed, normal-appearing collagen fibrils. Beneath this region, a broad zone of electron-dense elastotic material is evident. There are no data that demonstrate how newly synthesized or degraded, previously existing elastic fibers contribute to this material. Abnormal collagen fibrils can be admixed with the elastotic substance. Other studies show changes in the type III:I collagen ratio and an increase in glycosaminoglycans. Fibroblasts appear to be metabolically active. It is not clear whether this is a transient response to the UVR or whether there is a change in cell phenotype that can be retained in vitro. The mechanisms for the altered connective tissue responses are not understood. Dermal vessels become dilated, leaky, and accumulate excessive basement membrane-like material. Inflammatory cells collect around the vessels; mast cells are increased and may show evidence of degranulation and apparent physical associations with fibroblasts. Although the nature of this relationship is unknown, it is a common observation in other disorders in which fibrosis occurs.
Sunburn is UVR-induced erythema of the skin caused by vasodilatation of dermal vessels. This may be mediated through cyclo-oxygenase and lipoxygenase products of arachidonic acid.
Generation of the prostaglandins associated with UVB erythema produced within the first 6 to 12 hours can be blocked by topical nonsteroidal anti-inflammatory agents such as indomethacin. These anti-inflammatory agents, however, cannot inhibit the delayed, post 24-hour erythema that is modulated by lipoxygenase products. The time-dependent release of varying mediators during the UV-induced inflammatory process underscores the need for further exploration into selective inhibitors of both the cyclo-oxygenase and lipoxygenase pathways in the prevention and treatment of sunburn erythema.
Also associated with UVR irradiation of human skin is the appearance of dyskeratotic keratinocytes, known as sunburn cells, in the superficial layers of the epidermis. The mechanisms of the development of these cells are still unclear and warrant further exploration.
Tanning is the term applied to the increase in melanin pigmentation following UVR exposure. It is mediated by a combination of immediate pigment darkening (IPD) and delayed pigment darkening (DPD). IPD is caused by UVA and is due to photo-oxidation of preformed melanin. It is not protective against UVB erythema. DPD occurs about 72 hours after UVR exposure and does not afford much protection against UVB erythema and pyrimidine dimer formation. It is accompanied by an increase in the number of DOPA-positive melanocytes, an increase in the number and melanization of melanosomes, and an increase in dendricity of melanocytes.
The degree of protection afforded by melanin is unclear. Individuals with dark complexions are still susceptible to UVR-induced photodamage. UVR also increases the transfer of melanosomes from melanocytes to keratinocytes. Following UVR melanosomes diffusely distributed within keratinocytes collect above the nucleus, forming a "cap" over it. DPD occurs with either UVB or UVA. DPD induced by UVB is more protective against UVB erythema than is DPD induced by UVA. Both UVB- and UVA-induced DPD protect equally well against UVB dimer formation.
In addition to certain genetic and metabolic disorders that are precipitated by UVR, there are many photosensitive diseases of unknown cause. These include lupus erythematosus and polymorphous light eruption, which are elicited by certain wavelengths of the UVR spectrum. Photosensitivity disorders may also occur due to the interaction of UVR with many commonly used drugs, as well as chemicals used in industry and consumer products.
UVR modifies local and systemic immune responses, functionally alters Langerhans cells, and activates the T cell suppressor pathway. Soluble factors released from UV-irradiated epidermal cells also may be responsible for this altered immune response. In certain experimental systems, UVR-induced tumors transplanted into genetically identical animals are normally rejected. If these host animals are UV-irradiated before transplantation, the tumor will be accepted. These conclusions are based on animal studies. The role of UVR in the immunobiology of human skin cancer and, particularly, in susceptibility against certain cutaneous infectious diseases is unclear. More studies on the effect of UVR on human neoplastic and infectious disease are warranted.
There is extensive epidemiological evidence supporting the direct role sunlight plays in human skin cancer. Basal cell carcinomas (BCC), the most common skin cancers in Caucasians, are found primarily on sun-exposed areas such as the head and neck where a dose-response relationship exists. Furthermore, patients with skin cancer generally have decreased melanin pigmentation and associated photo-protection; people with light complexion and who sunburn easily have a higher incidence of tumors. There is even stronger evidence for the role of sunlight in causing SCC's. Although both BCC's and SCC's are more prevalent in geographic areas of high sun exposure, there is a much greater increase in SCC with decreasing latitude and increasing sun exposure. A reasonable correlation exists between sunlight exposure and melanoma, but the relationship is not as clear as with NMSC. It should be emphasized that the incidence of NMSC and melanomas has been steadily increasing. Unlike NMSC, melanomas occur most frequently on the upper back in males and lower extremities in females. Melanoma incidence does not follow a pattern of increased risk with cumulative UVR exposure whereas the incidence of NMSC does.
Extensive data also exist concerning UVR-induced skin cancer in experimental animals. In mice and guinea pigs, UVR induces mainly SCC whereas in rats both SCC and BCC are produced by repeated doses of UVR. In general, UVR induces SCC's in mice somewhat more effectively in young animals than in older ones. The cancer response is preceded by photodamage to the epidermal DNA, inflammation, epidermal hyperplasia, and dysplasia. Although there are several animal models in which chemical carcinogens can induce melanomas, the induction of melanomas by UVR has been very difficult if not impossible. Recent studies suggest that the opossum may be a reasonable model for UVR-induced melanomas.
Experiments in animals indicate that UVB is much more effective than UVA in causing NMSC. Nevertheless, UVA can induce DNA damage, erythema, and SCC in both pigmented and albino mice and in guinea pigs. Recent evidence suggests that the longer UVA wavelengths (UVA I:340 to 400 nm) of the UVA spectrum are less damaging than the shorter UVA wavelengths (UVA II:320 to 340 nm), but further research is needed to confirm this distinction.
The exposure of skin to UVB is essential for the endogenous production of vitamin D3. In areas of the world where there are inadequate levels of nutritionally available vitamin D, UVB is the only source. The relationship of sunshine to vitamin D3 and the normal growth and development of the skeleton is well known. Exposure of skin to UVR in the region of 290 to 315 nm is essential for the formation of vitamin D3 in the epidermis.
There is evidence that vitamin D3 synthesis is inhibited by the use of sunscreens. In the United States, this does not represent a health hazard for the pediatric population that receives adequate vitamin D supplementation in milk. In other countries this may not be the case. Deficiencies in elderly populations may exist.
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