STUDY - Technical - New Dacian's Medicine
Photosensitivity
and Other Skin Reactions to Light (2)
Translation Draft
We now move on to "more serious" things like the chronic effects of sun exposure and I'll start with nonmalignant ones.
Clinical features of sun-exposed photodamaged skin consist of wrinkles, spots, telangiectasis and a harsh, irregular appearance. It is not clear whether these changes, which are referred to by some photoaging or dermatoheliosis, represent an accelerated chronological ageing or a particularly separate and process. In the epidermis chronically exposed to the sun there is a thickening (acantosis) and a morphological heterogeneity in the basal cell layer. A higher but irregular content of melanosomes may be present in some keratocytes, indicating prolonged remaining of cells in the basal layer.
These structural changes can help explain the texture of tanned skin and coloring disorders in spots present in sun-damaged skin. Derm is the main site of chronic destruction associated with sun exposure, presenting itself in the form of massive growth of irregular groups of disordered elastic fibers, which occur as a result of prolonged, increased exposure of elastin genes. Collagen fibers are also abnormally grouped into the deeper dermis. Fibroblas are in increased numbers and show morphological signs suggesting activity. Degraded mastocytes may be present in the dermis, but their importance remains unclear. These morphological changes, both macro and microscopic, are characters of skin chronically exposed to the sun. Chromophores (chromophores), action spectra and specific biochemical events that orchestrate these changes are unknown.
It's the turn of the malignant chronic effects of sun exposure. One of the known major consequences of chronic skin exposure to sunlight is nonmelanomic skin cancer. The two types of nonmelanomic skin cancer sit le amus and spinal cell carcinoma. There are three major stages for cancer induction: initiation, promotion and progression. Chronic exposure of the skin to UV radiation sources causes initiation, a stage at which structural (mutagenic) changes in DNA cause an irreversible change in the target cell (keratocyte) that begins the tumor genesis process.
Exposure to a tumor originator is considered to be a necessary but insufficient stage in the malignant process, since the initial skin cells that are not exposed to tumor promoters do not generally develop tumors. The second stage in tumor development is promotion, a pluristadial process in which initiated cells are exposed to physical and chemical agents that cause epigenetic changes that culminate in the clonal expansion of the initial cells and cause the development, over a period of weeks to months, of benign growths, known as papillomas. In this respect, the importance of UV effects on the additional oncogene expression, such as "fos" and "jun", has been demonstrated in the appearance of papillomas. UV-B is a complete carcinogen, meaning it can function as both an initiator and promoter, leading to tumor induction.
Incomplete carcinogens can initiate tumourgenesis, but require additional skin exposure to tumor promoters to attract tumor production. The prototype tumor promoter is the 12-O-tettradecanoil-forbol-13-acetate forbol ester. Tumor promotion usually requires multiple exposures over time to cause a neoplasm. The final stage in the malignant process is the conversion of benign precursors into malignant lesions, a process believed to require additional genetic modification in already transformed cells.
Indeed, mutations of the "shaved" gene have been detected in a minority of nonmelanomic human skin cancers. Mutations of the Tumor Suppression Gene P53 also occur in human skin degraded by the sun. Solar exposure is thought to cause skin melanoma and nonmelanomic cancers, although the evidence is much more direct for its role in nonmelanomic cancers (baso and spinocellular carcinomas) than in melanomas.
Approximately 80% of nonmelanomic skin cancers occur on exposed body regions, including the face, neck and hands. Men with light skin who work outdoors are twice as likely as women to develop these cancers. White shears (e.g. Hispanics) have one-tenth of the risk of developing such cancers that open-skin individuals have. Blacks pose the lowest risk for all forms of skin cancer. Annually, millions of individuals (and the number is increasing) develop nonmelanomic skin cancers and the lifetime risk for a white individual to develop such a neoplasm is estimated at about 15%. There is a consensus that the incidence of nonmelanomic skin cancer in the population increases due to unclear causes.
The relationship between sun exposure and melanoma is less clear, but suggestive evidence indicates an association. melanomas sometimes develop in the years of adolescence, indicating that the latency period for tumor growth is less than that of nonmelanomas. Melanomas are among the fastest human malignant proliferations. Epidemiological studies on immigrants of similar ethnic origin indicate that individuals born in one region or those who immigrated to the same area before the age of 10 have higher rates, by age group, of the development of a melanoma than those who came later.
Therefore, it is acceptable to conclude that life in a sunny climate from birth or early childhood increases the risk of melanoma. In general, the risk does not correlate with cumulative sun exposure, but may be related to sequelae of childhood sun exposure. Thus, a bullous sunburn is associated with doubling the risk of melanoma in the region of this reaction.
In terms of immunological effects, exposure to solar radiation influences both local and systemic immune response. UV-B seems to be most effective in modifying the immune response, probably in relation to the ability of this energy to affect the presentation of the antigen in the skin, interacting with Langerhans epidermal cells. These dendritic cells derived from the bone marrow possess characteristic surface markers for monocytes and macrophages.
After skin exposure to erythemariogenic doses of UV-B, Langerhans cells undergo functional and morphological changes that lead to decreased allergic contact responses when applied to irradiated site. This low sensitization capacity is due to the induction of antigen-specific t lymphocytes. Indeed, while the immunosuppressive effect of irradiation is limited to haptene applied to the irradiated site, the net result is systemic immune suppression to that antigen due to the induction of suppressor T cells.
Higher doses of radiation give rise to decreased immunological responses introduced epicutaneously or intradermally in places far from the irradiated region. These suppressed responses are also associated with the induction of antigen-specific suppressor T lymphocytes and may be mediated by as yet undefined factors that are released by epidermal cells in the irradiated region. The implications of this generalized immune suppression with regard to altered susceptibility to skin cancers or infections remains to be defined.
UV-induced tumours are known to be antigenic and are rapidly rejected when transplanted (either by mistake). If tumors are transplanted into areas previously exposed to subcarcinogenic doses of UV-B, they are not rejected, but gradually increase to recipients. This inability to reject transplanted tumors is due to the development of suppressor T cells, which prevents rejection response. While the mechanism of tumor suppression is unknown, such a response may be an essential determinant of the risk of skin cancer in humans.
I will complete this post with some elements about diseases due to photosensitivity. The diagnosis of photosensitivity requires a careful history to define the duration of signs and symptoms, the length of time between exposure to sunlight and the appearance of subjective accusations and subjective changes of the skin. Age of onset can also be a useful clue (for example, acute photosensitivity in erythropoietic protoporphyry almost always begins in childhood, while chronic photosensitivity in late skin porphyria typically begins in the four and fifth decades of life).
A history of exposure to systemic and topical drugs and chemicals may provide important additional information. Many classes of medicines can cause photosensitivity, either on the basis of phototocxicity or photoallergy. Flavors, such as the musk contained in many cosmetics, are also powerful photosensitizers. Skin examination can also provide important clues.
Anatomical regions that are naturally protected from direct sunlight, such as hairy head skin, upper eyelids, retroauricular, infranasal and submentonary regions can be observed, while exposed regions exhibit characteristic features of the pathological process. These anatomical localization patterns are useful, but not infallible in making the diagnosis. For example, air-borne contact sensitizers that come into contact with the skin can produce dermatitis that can be difficult to distinguish from particularly photosensitivity, despite the fact that such a substance can trigger skin reactivity in regions protected by direct sunlight.
Many dermatological conditions can be caused or aggravated by light. Diseases due to photosensitivity are classified by type of disease in: 1. genetic (erythropoietic porphyria, erythropoietic protoporphyry, late familial skin porphyria, variegata porphyria, hepatoerythroytic porphyria, albinism, xeroderma pigmentosum, Rothmund-Thompson disease, Bloom disease, Cockayne disease, phenylcetonuria), 2. metabolic (sporadic late skin porphyria, Hartnup disease, Kwashirkor, pelagra, carcinoid syndrome, pseudoforfiria), 3. phototoxic (medicines) and 4. (medicines, plants, food), 5. immediate photoallergic (solar urticaria) and 6. (drug photoallergy and persistent reaction to light/ chronic actinic dermatitis), 7. neoplastic and degenerative (photoaging, actinic keratoses, basal cell carcinoma), 8. idiopathic (polymorphic light rash, aestival hydroa, actinic reticuloid) and 9. photoagravate (systemic or subacute lupus erythematosus, dermatomyositis, foliaceus pemfigus, herpes simplex, actinic lichen plan, vulgar/ summer acne and transient acantolitic dermatosis).
The role of light in challenging these responses may be dependent on genetic abnormalities, ranging from well-described defects in DNA repair in xeroderma pigmentosum, to hereditary abnormalities in the synthesis of hem, which characterize porphyria. In certain photosensitivity diseases chromophore has been identified, while in most, the energy absorbing agent is unknown.
And, that's enough for today!
We now move on to "more serious" things like the chronic effects of sun exposure and I'll start with nonmalignant ones.
Clinical features of sun-exposed photodamaged skin consist of wrinkles, spots, telangiectasis and a harsh, irregular appearance. It is not clear whether these changes, which are referred to by some photoaging or dermatoheliosis, represent an accelerated chronological ageing or a particularly separate and process. In the epidermis chronically exposed to the sun there is a thickening (acantosis) and a morphological heterogeneity in the basal cell layer. A higher but irregular content of melanosomes may be present in some keratocytes, indicating prolonged remaining of cells in the basal layer.
These structural changes can help explain the texture of tanned skin and coloring disorders in spots present in sun-damaged skin. Derm is the main site of chronic destruction associated with sun exposure, presenting itself in the form of massive growth of irregular groups of disordered elastic fibers, which occur as a result of prolonged, increased exposure of elastin genes. Collagen fibers are also abnormally grouped into the deeper dermis. Fibroblas are in increased numbers and show morphological signs suggesting activity. Degraded mastocytes may be present in the dermis, but their importance remains unclear. These morphological changes, both macro and microscopic, are characters of skin chronically exposed to the sun. Chromophores (chromophores), action spectra and specific biochemical events that orchestrate these changes are unknown.
It's the turn of the malignant chronic effects of sun exposure. One of the known major consequences of chronic skin exposure to sunlight is nonmelanomic skin cancer. The two types of nonmelanomic skin cancer sit le amus and spinal cell carcinoma. There are three major stages for cancer induction: initiation, promotion and progression. Chronic exposure of the skin to UV radiation sources causes initiation, a stage at which structural (mutagenic) changes in DNA cause an irreversible change in the target cell (keratocyte) that begins the tumor genesis process.
Exposure to a tumor originator is considered to be a necessary but insufficient stage in the malignant process, since the initial skin cells that are not exposed to tumor promoters do not generally develop tumors. The second stage in tumor development is promotion, a pluristadial process in which initiated cells are exposed to physical and chemical agents that cause epigenetic changes that culminate in the clonal expansion of the initial cells and cause the development, over a period of weeks to months, of benign growths, known as papillomas. In this respect, the importance of UV effects on the additional oncogene expression, such as "fos" and "jun", has been demonstrated in the appearance of papillomas. UV-B is a complete carcinogen, meaning it can function as both an initiator and promoter, leading to tumor induction.
Incomplete carcinogens can initiate tumourgenesis, but require additional skin exposure to tumor promoters to attract tumor production. The prototype tumor promoter is the 12-O-tettradecanoil-forbol-13-acetate forbol ester. Tumor promotion usually requires multiple exposures over time to cause a neoplasm. The final stage in the malignant process is the conversion of benign precursors into malignant lesions, a process believed to require additional genetic modification in already transformed cells.
Indeed, mutations of the "shaved" gene have been detected in a minority of nonmelanomic human skin cancers. Mutations of the Tumor Suppression Gene P53 also occur in human skin degraded by the sun. Solar exposure is thought to cause skin melanoma and nonmelanomic cancers, although the evidence is much more direct for its role in nonmelanomic cancers (baso and spinocellular carcinomas) than in melanomas.
Approximately 80% of nonmelanomic skin cancers occur on exposed body regions, including the face, neck and hands. Men with light skin who work outdoors are twice as likely as women to develop these cancers. White shears (e.g. Hispanics) have one-tenth of the risk of developing such cancers that open-skin individuals have. Blacks pose the lowest risk for all forms of skin cancer. Annually, millions of individuals (and the number is increasing) develop nonmelanomic skin cancers and the lifetime risk for a white individual to develop such a neoplasm is estimated at about 15%. There is a consensus that the incidence of nonmelanomic skin cancer in the population increases due to unclear causes.
The relationship between sun exposure and melanoma is less clear, but suggestive evidence indicates an association. melanomas sometimes develop in the years of adolescence, indicating that the latency period for tumor growth is less than that of nonmelanomas. Melanomas are among the fastest human malignant proliferations. Epidemiological studies on immigrants of similar ethnic origin indicate that individuals born in one region or those who immigrated to the same area before the age of 10 have higher rates, by age group, of the development of a melanoma than those who came later.
Therefore, it is acceptable to conclude that life in a sunny climate from birth or early childhood increases the risk of melanoma. In general, the risk does not correlate with cumulative sun exposure, but may be related to sequelae of childhood sun exposure. Thus, a bullous sunburn is associated with doubling the risk of melanoma in the region of this reaction.
In terms of immunological effects, exposure to solar radiation influences both local and systemic immune response. UV-B seems to be most effective in modifying the immune response, probably in relation to the ability of this energy to affect the presentation of the antigen in the skin, interacting with Langerhans epidermal cells. These dendritic cells derived from the bone marrow possess characteristic surface markers for monocytes and macrophages.
After skin exposure to erythemariogenic doses of UV-B, Langerhans cells undergo functional and morphological changes that lead to decreased allergic contact responses when applied to irradiated site. This low sensitization capacity is due to the induction of antigen-specific t lymphocytes. Indeed, while the immunosuppressive effect of irradiation is limited to haptene applied to the irradiated site, the net result is systemic immune suppression to that antigen due to the induction of suppressor T cells.
Higher doses of radiation give rise to decreased immunological responses introduced epicutaneously or intradermally in places far from the irradiated region. These suppressed responses are also associated with the induction of antigen-specific suppressor T lymphocytes and may be mediated by as yet undefined factors that are released by epidermal cells in the irradiated region. The implications of this generalized immune suppression with regard to altered susceptibility to skin cancers or infections remains to be defined.
UV-induced tumours are known to be antigenic and are rapidly rejected when transplanted (either by mistake). If tumors are transplanted into areas previously exposed to subcarcinogenic doses of UV-B, they are not rejected, but gradually increase to recipients. This inability to reject transplanted tumors is due to the development of suppressor T cells, which prevents rejection response. While the mechanism of tumor suppression is unknown, such a response may be an essential determinant of the risk of skin cancer in humans.
I will complete this post with some elements about diseases due to photosensitivity. The diagnosis of photosensitivity requires a careful history to define the duration of signs and symptoms, the length of time between exposure to sunlight and the appearance of subjective accusations and subjective changes of the skin. Age of onset can also be a useful clue (for example, acute photosensitivity in erythropoietic protoporphyry almost always begins in childhood, while chronic photosensitivity in late skin porphyria typically begins in the four and fifth decades of life).
A history of exposure to systemic and topical drugs and chemicals may provide important additional information. Many classes of medicines can cause photosensitivity, either on the basis of phototocxicity or photoallergy. Flavors, such as the musk contained in many cosmetics, are also powerful photosensitizers. Skin examination can also provide important clues.
Anatomical regions that are naturally protected from direct sunlight, such as hairy head skin, upper eyelids, retroauricular, infranasal and submentonary regions can be observed, while exposed regions exhibit characteristic features of the pathological process. These anatomical localization patterns are useful, but not infallible in making the diagnosis. For example, air-borne contact sensitizers that come into contact with the skin can produce dermatitis that can be difficult to distinguish from particularly photosensitivity, despite the fact that such a substance can trigger skin reactivity in regions protected by direct sunlight.
Many dermatological conditions can be caused or aggravated by light. Diseases due to photosensitivity are classified by type of disease in: 1. genetic (erythropoietic porphyria, erythropoietic protoporphyry, late familial skin porphyria, variegata porphyria, hepatoerythroytic porphyria, albinism, xeroderma pigmentosum, Rothmund-Thompson disease, Bloom disease, Cockayne disease, phenylcetonuria), 2. metabolic (sporadic late skin porphyria, Hartnup disease, Kwashirkor, pelagra, carcinoid syndrome, pseudoforfiria), 3. phototoxic (medicines) and 4. (medicines, plants, food), 5. immediate photoallergic (solar urticaria) and 6. (drug photoallergy and persistent reaction to light/ chronic actinic dermatitis), 7. neoplastic and degenerative (photoaging, actinic keratoses, basal cell carcinoma), 8. idiopathic (polymorphic light rash, aestival hydroa, actinic reticuloid) and 9. photoagravate (systemic or subacute lupus erythematosus, dermatomyositis, foliaceus pemfigus, herpes simplex, actinic lichen plan, vulgar/ summer acne and transient acantolitic dermatosis).
The role of light in challenging these responses may be dependent on genetic abnormalities, ranging from well-described defects in DNA repair in xeroderma pigmentosum, to hereditary abnormalities in the synthesis of hem, which characterize porphyria. In certain photosensitivity diseases chromophore has been identified, while in most, the energy absorbing agent is unknown.
And, that's enough for today!
Don't forget the weekend's
coming... or that it's started!!! Be good, fun, useful, full of
understanding, love and gratitude!
Dorin, Merticaru