STUDY - Technical - New Dacian's Medicine
Photosensitivity
and Other Skin Reactions to Light (3)
Translation Draft
With this post I will be able to complete this group of skin signs (skin disorders) and, of course, to "fill in" the file "newmedicine.pdf". But let's get to work!
I stuck to the polymorphic rash. After sunburn, the most common type of photosensitivity disease is polymorphic light rash, the mechanism of which is unknown. Many affected individuals never seek medical attention, as the condition is often transient, becoming manifest every spring to initial sun exposure, but then spontaneously disappearing with further exposure, a phenomenon known as "riding". Major manifestations of polymorphic light rash include pruriginous erythematous papules (often intensely itchy), which can merge into plaques on exposed areas of the face and arms or in other areas, making distribution into plaques and non-homogeneous.
The diagnosis can be confirmed by skin biopsy and by performing phototesting procedures, in which the skin is exposed to multiple erythematogen doses of UV-A and UV-B. The spectrum of action for polymorphic eruption to light is usually in these portions of the solar spectrum. Treatment of this disease includes induction of "caliation" by controlled administration of UV light, either alone or in association with photosensitizers like psoralens.
Let's move on to phototoxicity and photoallergy! These photosensitivity disorders are related to topical or systemic administration of medicines and other chemicals. Both require the absorption of energy by a drug or chemical, leading to the production of an excited photosensitizer, which can transfer the absorbed energy to a neighborhood molecule or molecular oxygen, thus generating destructive tissue chemicals. Phototoxicity is a non-immunological reaction caused by drugs and chemicals, some of which are represented by: 1. coal tar derivatives (acrydin, anthracene and phenantren), 2. medicines (amiodarone, dacarbazine, fluoroquinolone, 5-fuoroquinolone, furosemide, nadidixic acid, phenothiazine, psoraleni, retinoids, sulfonamides, sulfonilurea, tetracyclines, thiazides and vinblastin) and 3. dyes (antracinone, eosine, methylene blue and bengal pink). Common clinical manifestations include sunburn-like erythema that quickly descuats or exfoliates within a few days. In addition, edema, blisters and bubbles may occur.
Photoallergy is special in that the immune system participates in the pathological process. The excited sensitizer can create very unstable haptenic free radicals that covalently bind to macromolecules to form a functional antigen capable of causing a delayed hypersensitivity response. Some of these drugs and chemicals that produce photoallergy are represented by: 1. antibiotics (sulfonamides), 2. antifungal (fenticlor, jadit and multifungin), 3. diuretics (thiazides), 4. flavors (mosc, 6-methyl-coumarin and vegetable oleorasins), 5. halogenated salicylates (bitionol, tetrachlorsalicylanimide and tribromsalicylanimida), 6. NSAID (pyroxicam), 7. phenothiazides (chlorpromazine, promethazine and sulfonilurea), 8. solar screens (para-aminobenzoic acid and ester) and 9. bleaching agents (stilbens).
Clinical manifestations differ typically from those of phototoxicity in that an intensely itchy eczema tordinous dermatitis tends to predominate and evolves towards changes in lichenification, infiltration, "tanned skin" in solar-exposed areas. A small subgroup (maybe 5-10%) of patients with photoallergy may develop an exceptional persistent hypersensitivity to light, even when the triggering drug or chemical has been identified and eliminated. Known as the persistent reaction to light, it can be debilitating for years. Some authors have used the term chronic actinic dermatitis to encompass these chronic hyperresponsive states.
Diagnostic confirmation of phototoxicity and photoallergy can often be obtained using phototesting procedures. In patients suspected of phototoxicity, determining the minimum erythematogenic dose (EMD) while the patient is exposed to a suspected agent and then repeating the DEM after discontinuation of the agent may provide an indication for the identification of the drug or causative chemical. Photoepicutaneous tests can be done to confirm the diagnosis of photoallergy. This is a simple variant of the usual epicutan test, in which a number of known photoallergens are applied to the skin in duplicate and a set is irradiated with a suberythematous dose of UV-A.
The occurrence of eczema to change in regions exposed to sensitizing and light is a positive result. The characteristic anomaly in patients with persistent reaction to light is a low threshold to UV-B-induced erythema. Patients with chronic actinic dermatitis may have a wide spectrum of UV hyperresponsiveness. Treatment of photosensitivity to medicines consists, as a priority, of eliminating exposure to the chemical agents responsible for the reaction and minimizing sun exposure. Acute symptoms of phototoxicity can be improved by refreshing wet compresses, topical glucocorticoids and systemically administered nonsteroidal anti-inflammatory agents.
In severely affected individuals, a rapidly decreasing cure of systemic glucocorticoids may be useful. Judicious use of painkillers may be necessary. Photoallergic reactions require similar therapeutic conduct. Furthermore, individuals suffering from persistent light reactivity should be meticulously protected from exposure to light. In some patients in whom chronically administered and high-dose systemic glucocorticoids cause unacceptable risks, the use of cytotoxic agents, such as azatiopina or cyclophosphamide, is required.
Porphyria are a group of diseases that have in common various disorders in the synthesis of hem. Hem is an iron-cheled tetrapirol or porphyrin, and porphyrins that are not chelated with metals are powerful photosensitizers that absorb light intensely in both short (400-410 nm) and long (580-650 nm) portions of the visible spectrum. The hem cannot be reused and must be synthesized continuously, and the two compartments of the body that have the greatest production capacities are the bone marrow and the liver.
Appropriately, porphyria originate in one or the other of these organs, with the end result of excessive endogenous production of highly photosensitizing porphyrins. Porphyrins circulate in the bloodstream and diffuse into the skin, where they absorb solar energy, become photo-exciting and cause skin photosensitivity. The mechanism of porphyrin photosensitivity is known to be a photodynamic or oxygen-dependent reaction and is mediated by reactive oxygen species, such as superoxide anions.
Late skin porphyria is the most common type of porphyria and is associated with low activity of the enzyme uroporphyrinogendecarboxylase, in conjunction with a number of genetic mutations. There are two main types of late skin porphyria: sporadic or acquired type, generally found in ethanol-consuming individuals or receiving estrogens, and hereditary type, in which there is dominant autosomal transmission of deficient enzyme activity. Both forms are associated with increased iron deposits.
In both types of late skin porphyria the predominant trait is a chronic photosensitivity, characterized by increased fragility of sun-exposed skin, especially areas subjected to repeated trauma, such as the dorsal face of the hands, forearms, face and ears. Predominant skin lesions are blisters and bubbles that break, producing wet erosions, often with a hemorrhagic base and that heal slowly, with crust formation and violet coloration of the affected skin. Hypertricosis, non-homogeneous pigmentation changes and scleroderma-like pain are associated symptoms.
Biochemical compliance of the diagnosis can be obtained by measuring the urinary excretion of porphyrins, measuring plasma porphyrin and by determining uroporphyrinogen-decarboxylase. Multiple mutations of the uroporphyrinogen-decarboxylase gene, including exons escaped and substituted by bases, have been identified in human populations. Treatment consists of repeated phlebotomies to reduce liver reserves of iron and/ or low intermittent doses of antimalaria, chloroquine and hydroxychloroquine. Long-term remission of the disease can be achieved if the patient discontinues exposure to porphyrinogen agents.
Erythropoietic protoporphyry originates in the bone marrow and is due to a decrease in the mitochondrial enzyme ferochelatase, following a number of genetic mutations. Major clinical features include acute photosensitivity, characterized by subjective signs of sun-exposed skin that often occur during or immediately after exposure. Skin swelling and, after repeated episodes, a cerous scarring may be associated. The diagnosis is confirmed by highlighting elevated levels of free erythrocytic porphyrin. Detection of increased plasma protoporphyrin helps to differentiate from lead poisoning and ferriprivate anaemia, in both appearing increased erythrocytic protoporphyrins in the absence of skin photosensitivity and increased plasma protoporphyrin. Treatment consists in reducing sun exposure and oral administration of beta-carotene carotenoid, which is an effective captor of free radicals. This drug increases the tolerance to sun exposure of many affected individuals, although it has no effect on the deficiency of ferochelatosis.
Let's talk about photoprotection now. Because skin photosensitivity is caused by exposure to sunlight, it follows that avoiding the sun would eliminate these disorders. Unfortunately, social pressures make this alternative impractical for most individuals, leading to the search for a better approach to photoprotection. Natural photoprotection is provided by structural proteins in the epidermis, especially keratin and melanin. The amount of melanin and its distribution in cells is genetically regulated and individuals with darker skin have a lower risk of developing skin cancers. Other forms of photoprotection include clothing and solar screens. Clothing consisting of tightly woven textiles, regardless of colour, provides substantial protection.
Wide-brimmed hats, long sleeves and long pants reduce direct exposure to light. Solar screens are of two types, chemical and physical. Chemical agent screens are chromophores that absorb energy in UV-A and/ or UV-B regions, thereby diminishing the absorption of photons by the skin. Solar screens are evaluated for their protective effect by the sunscreen factor (FPS). FPS is simply the ratio of the time it takes to produce solar burn erythema with and without sunscreen application. FPS levels of 15 or more provide effective UV-B and, to a lesser degree, UV-A protection. Major categories of chemical solar screens include p-aminobenzoic acid and its esteria, benzofeno, antranilates, cinnamats and salicylates.
Physical solar screens are opaque light-light mixtures containing metallic particles, such as titanium oxide, that scatter light, thus reducing the absorption of photons by the skin. In addition to the absorption of light, a decisive determinant of the photoprotective effect of solar screens is their ability to remain on the skin, a property called nounity. In general, p-aminobesoic acid in the formula with humidified vehicles provides the best nounity. Photoprotection can also be achieved by limiting the time of exposure during the day. Since the majority of an individual's total lifetime solar exposure can occur up to 18 years, it is important to educate parents and young children about the risks of solar radiation.
Simply eliminating exposure to midday hours will bring a substantial reduction in lifetime exposure to UV-B.
I'll finish with phototherapy and photochemisty. UV radiation can also be used therapeutically. Administration of UV-B isolated or in combination with topically applied compounds may induce remissions in psoriasis and atopic dermatitis. Photochemy in which UV-A are administered in combination with topical or systemically applied psoraleni (PUVA) is also effective in the treatment of psoriasis, in the early stages of T-cell skin lymphomas and in vitiligo. Psoralists are tricyclic furocumarines which, if interspersed in DNA and exposed to UV-A, produce monofunctional bonds in pyrimidine bases and ultimately form cross-links in DNA. These structural changes are considered to decrease DNA synthesis and are related to the improvement that occurs in psoriasis.
The reason why photochemisty is effective in T-cell skin lymphomas is not clear. In addition to its effects on DNA, photochemisty also stimulates the synthesis of melanin and this is the reason for its use in the disease with depigmentation, vitiligo. 8-methoxypsoralen administered orally and UV-A appear to be effective in this regard, but up to 100 treatments may be needed over 12-18 months to achieve satisfactory repigmentation. Major side effects of UV-B and PUVA photochemistry are due to the cumulative effects of photonic absorption and include dry skin, actinic keratoses and an increased risk of nonmelanomic skin cancer. Despite these risks, the therapeutic index of these modalities is relatively acceptable.
Ready for today!
With this post I will be able to complete this group of skin signs (skin disorders) and, of course, to "fill in" the file "newmedicine.pdf". But let's get to work!
I stuck to the polymorphic rash. After sunburn, the most common type of photosensitivity disease is polymorphic light rash, the mechanism of which is unknown. Many affected individuals never seek medical attention, as the condition is often transient, becoming manifest every spring to initial sun exposure, but then spontaneously disappearing with further exposure, a phenomenon known as "riding". Major manifestations of polymorphic light rash include pruriginous erythematous papules (often intensely itchy), which can merge into plaques on exposed areas of the face and arms or in other areas, making distribution into plaques and non-homogeneous.
The diagnosis can be confirmed by skin biopsy and by performing phototesting procedures, in which the skin is exposed to multiple erythematogen doses of UV-A and UV-B. The spectrum of action for polymorphic eruption to light is usually in these portions of the solar spectrum. Treatment of this disease includes induction of "caliation" by controlled administration of UV light, either alone or in association with photosensitizers like psoralens.
Let's move on to phototoxicity and photoallergy! These photosensitivity disorders are related to topical or systemic administration of medicines and other chemicals. Both require the absorption of energy by a drug or chemical, leading to the production of an excited photosensitizer, which can transfer the absorbed energy to a neighborhood molecule or molecular oxygen, thus generating destructive tissue chemicals. Phototoxicity is a non-immunological reaction caused by drugs and chemicals, some of which are represented by: 1. coal tar derivatives (acrydin, anthracene and phenantren), 2. medicines (amiodarone, dacarbazine, fluoroquinolone, 5-fuoroquinolone, furosemide, nadidixic acid, phenothiazine, psoraleni, retinoids, sulfonamides, sulfonilurea, tetracyclines, thiazides and vinblastin) and 3. dyes (antracinone, eosine, methylene blue and bengal pink). Common clinical manifestations include sunburn-like erythema that quickly descuats or exfoliates within a few days. In addition, edema, blisters and bubbles may occur.
Photoallergy is special in that the immune system participates in the pathological process. The excited sensitizer can create very unstable haptenic free radicals that covalently bind to macromolecules to form a functional antigen capable of causing a delayed hypersensitivity response. Some of these drugs and chemicals that produce photoallergy are represented by: 1. antibiotics (sulfonamides), 2. antifungal (fenticlor, jadit and multifungin), 3. diuretics (thiazides), 4. flavors (mosc, 6-methyl-coumarin and vegetable oleorasins), 5. halogenated salicylates (bitionol, tetrachlorsalicylanimide and tribromsalicylanimida), 6. NSAID (pyroxicam), 7. phenothiazides (chlorpromazine, promethazine and sulfonilurea), 8. solar screens (para-aminobenzoic acid and ester) and 9. bleaching agents (stilbens).
Clinical manifestations differ typically from those of phototoxicity in that an intensely itchy eczema tordinous dermatitis tends to predominate and evolves towards changes in lichenification, infiltration, "tanned skin" in solar-exposed areas. A small subgroup (maybe 5-10%) of patients with photoallergy may develop an exceptional persistent hypersensitivity to light, even when the triggering drug or chemical has been identified and eliminated. Known as the persistent reaction to light, it can be debilitating for years. Some authors have used the term chronic actinic dermatitis to encompass these chronic hyperresponsive states.
Diagnostic confirmation of phototoxicity and photoallergy can often be obtained using phototesting procedures. In patients suspected of phototoxicity, determining the minimum erythematogenic dose (EMD) while the patient is exposed to a suspected agent and then repeating the DEM after discontinuation of the agent may provide an indication for the identification of the drug or causative chemical. Photoepicutaneous tests can be done to confirm the diagnosis of photoallergy. This is a simple variant of the usual epicutan test, in which a number of known photoallergens are applied to the skin in duplicate and a set is irradiated with a suberythematous dose of UV-A.
The occurrence of eczema to change in regions exposed to sensitizing and light is a positive result. The characteristic anomaly in patients with persistent reaction to light is a low threshold to UV-B-induced erythema. Patients with chronic actinic dermatitis may have a wide spectrum of UV hyperresponsiveness. Treatment of photosensitivity to medicines consists, as a priority, of eliminating exposure to the chemical agents responsible for the reaction and minimizing sun exposure. Acute symptoms of phototoxicity can be improved by refreshing wet compresses, topical glucocorticoids and systemically administered nonsteroidal anti-inflammatory agents.
In severely affected individuals, a rapidly decreasing cure of systemic glucocorticoids may be useful. Judicious use of painkillers may be necessary. Photoallergic reactions require similar therapeutic conduct. Furthermore, individuals suffering from persistent light reactivity should be meticulously protected from exposure to light. In some patients in whom chronically administered and high-dose systemic glucocorticoids cause unacceptable risks, the use of cytotoxic agents, such as azatiopina or cyclophosphamide, is required.
Porphyria are a group of diseases that have in common various disorders in the synthesis of hem. Hem is an iron-cheled tetrapirol or porphyrin, and porphyrins that are not chelated with metals are powerful photosensitizers that absorb light intensely in both short (400-410 nm) and long (580-650 nm) portions of the visible spectrum. The hem cannot be reused and must be synthesized continuously, and the two compartments of the body that have the greatest production capacities are the bone marrow and the liver.
Appropriately, porphyria originate in one or the other of these organs, with the end result of excessive endogenous production of highly photosensitizing porphyrins. Porphyrins circulate in the bloodstream and diffuse into the skin, where they absorb solar energy, become photo-exciting and cause skin photosensitivity. The mechanism of porphyrin photosensitivity is known to be a photodynamic or oxygen-dependent reaction and is mediated by reactive oxygen species, such as superoxide anions.
Late skin porphyria is the most common type of porphyria and is associated with low activity of the enzyme uroporphyrinogendecarboxylase, in conjunction with a number of genetic mutations. There are two main types of late skin porphyria: sporadic or acquired type, generally found in ethanol-consuming individuals or receiving estrogens, and hereditary type, in which there is dominant autosomal transmission of deficient enzyme activity. Both forms are associated with increased iron deposits.
In both types of late skin porphyria the predominant trait is a chronic photosensitivity, characterized by increased fragility of sun-exposed skin, especially areas subjected to repeated trauma, such as the dorsal face of the hands, forearms, face and ears. Predominant skin lesions are blisters and bubbles that break, producing wet erosions, often with a hemorrhagic base and that heal slowly, with crust formation and violet coloration of the affected skin. Hypertricosis, non-homogeneous pigmentation changes and scleroderma-like pain are associated symptoms.
Biochemical compliance of the diagnosis can be obtained by measuring the urinary excretion of porphyrins, measuring plasma porphyrin and by determining uroporphyrinogen-decarboxylase. Multiple mutations of the uroporphyrinogen-decarboxylase gene, including exons escaped and substituted by bases, have been identified in human populations. Treatment consists of repeated phlebotomies to reduce liver reserves of iron and/ or low intermittent doses of antimalaria, chloroquine and hydroxychloroquine. Long-term remission of the disease can be achieved if the patient discontinues exposure to porphyrinogen agents.
Erythropoietic protoporphyry originates in the bone marrow and is due to a decrease in the mitochondrial enzyme ferochelatase, following a number of genetic mutations. Major clinical features include acute photosensitivity, characterized by subjective signs of sun-exposed skin that often occur during or immediately after exposure. Skin swelling and, after repeated episodes, a cerous scarring may be associated. The diagnosis is confirmed by highlighting elevated levels of free erythrocytic porphyrin. Detection of increased plasma protoporphyrin helps to differentiate from lead poisoning and ferriprivate anaemia, in both appearing increased erythrocytic protoporphyrins in the absence of skin photosensitivity and increased plasma protoporphyrin. Treatment consists in reducing sun exposure and oral administration of beta-carotene carotenoid, which is an effective captor of free radicals. This drug increases the tolerance to sun exposure of many affected individuals, although it has no effect on the deficiency of ferochelatosis.
Let's talk about photoprotection now. Because skin photosensitivity is caused by exposure to sunlight, it follows that avoiding the sun would eliminate these disorders. Unfortunately, social pressures make this alternative impractical for most individuals, leading to the search for a better approach to photoprotection. Natural photoprotection is provided by structural proteins in the epidermis, especially keratin and melanin. The amount of melanin and its distribution in cells is genetically regulated and individuals with darker skin have a lower risk of developing skin cancers. Other forms of photoprotection include clothing and solar screens. Clothing consisting of tightly woven textiles, regardless of colour, provides substantial protection.
Wide-brimmed hats, long sleeves and long pants reduce direct exposure to light. Solar screens are of two types, chemical and physical. Chemical agent screens are chromophores that absorb energy in UV-A and/ or UV-B regions, thereby diminishing the absorption of photons by the skin. Solar screens are evaluated for their protective effect by the sunscreen factor (FPS). FPS is simply the ratio of the time it takes to produce solar burn erythema with and without sunscreen application. FPS levels of 15 or more provide effective UV-B and, to a lesser degree, UV-A protection. Major categories of chemical solar screens include p-aminobenzoic acid and its esteria, benzofeno, antranilates, cinnamats and salicylates.
Physical solar screens are opaque light-light mixtures containing metallic particles, such as titanium oxide, that scatter light, thus reducing the absorption of photons by the skin. In addition to the absorption of light, a decisive determinant of the photoprotective effect of solar screens is their ability to remain on the skin, a property called nounity. In general, p-aminobesoic acid in the formula with humidified vehicles provides the best nounity. Photoprotection can also be achieved by limiting the time of exposure during the day. Since the majority of an individual's total lifetime solar exposure can occur up to 18 years, it is important to educate parents and young children about the risks of solar radiation.
Simply eliminating exposure to midday hours will bring a substantial reduction in lifetime exposure to UV-B.
I'll finish with phototherapy and photochemisty. UV radiation can also be used therapeutically. Administration of UV-B isolated or in combination with topically applied compounds may induce remissions in psoriasis and atopic dermatitis. Photochemy in which UV-A are administered in combination with topical or systemically applied psoraleni (PUVA) is also effective in the treatment of psoriasis, in the early stages of T-cell skin lymphomas and in vitiligo. Psoralists are tricyclic furocumarines which, if interspersed in DNA and exposed to UV-A, produce monofunctional bonds in pyrimidine bases and ultimately form cross-links in DNA. These structural changes are considered to decrease DNA synthesis and are related to the improvement that occurs in psoriasis.
The reason why photochemisty is effective in T-cell skin lymphomas is not clear. In addition to its effects on DNA, photochemisty also stimulates the synthesis of melanin and this is the reason for its use in the disease with depigmentation, vitiligo. 8-methoxypsoralen administered orally and UV-A appear to be effective in this regard, but up to 100 treatments may be needed over 12-18 months to achieve satisfactory repigmentation. Major side effects of UV-B and PUVA photochemistry are due to the cumulative effects of photonic absorption and include dry skin, actinic keratoses and an increased risk of nonmelanomic skin cancer. Despite these risks, the therapeutic index of these modalities is relatively acceptable.
Ready for today!
A BEST weekend!
Don't forget the weekend's
coming... or that it's started!!! Be good, fun, useful, full of
understanding, love and gratitude!
Dorin, Merticaru