VITAMINS IN DERMATOLOGY

Vitamins are biologically active organic compounds, which are indispensable for the normal functions of the body. They have no direct function as an energy source or as structural tissue components,but in most cases act as coenzymes in various enzyme systems.

Vitamin AVitamin A (retinol) is a cyclic polyene alcohol present in yellow and green vegetables, egg yolk, butter, liver and fi sh oils Carotene occurs in fruits, carrots and green vegetables, and is absorbed and converted to vitamin A in the body. The recommended daily allowance is 5000 i.u. (equivalent to 6000–12 000 i.u. -carotene). The plasma level in normal adults is about 600 ng/mL[2]. Vitamin A is mobilized from liver stores and transported in plasma, in which it is bound to retinol-binding protein [3]. Vitamin A is essential for the reproductive system, bone formation, vision and epithelial tissues [4]. In vitro studies on human keratinocytes have shown that vitamin A affects their growth and differentiation [5]. In human volunteers, 150 000 i.u. daily of vitamin A produced demonstrable retardation of keratinocyte maturation [6]. Skin disorders with abnormal keratinization, such as ichthyosis, pityriasis rubra pilaris and Darier’s disease, havebeen treated with high doses of oral vitamin A. There is a risk of intoxication by such treatment and stereoisomers of retinoic acid are now used instead .Vitamin A defi ciencyVitamin A defi ciency is seldom seen in the Western world today. It is observed mainly in diseases causing malabsorption and is often associated with deficiency of other fat-soluble vitamins.Clinical features. Classical manifestations of vitamin A defi ciency include xerophthalmia, follicular hyperkeratosis and generalized xerosis [8]. Follicular papules are seen especially on the dorsal and lateral areas of the extremities, so-called phrynoderma. Histologically, there is lamellated hyperkeratosis around the hair follicleswith keratinous plugs and atrophy of the sebaceous glands [9]. Diagnosis is confi rmed by the fi nding of a low vitamin A level in blood and a positive response to vitamin A supplementation. Zinc defi ciency may lead to vitamin A defi ciency as zinc acts on the retinol-binding protein, which is the transport protein for vitamin A and which is indispensable for mobilization of the vitamin from the liver. Furthermore, zinc acts on the oxidation– reduction interconversion of vitamin A (alcohol dehydrogenase is a zinc metalloenzyme). Lack of zinc may provoke symptoms of vitamin A defi ciency [10], and night blindness in alcoholics maybe due to a combined lack of vitamin A and zinc [11].Vitamin A intoxicationAetiology. Chronic hypervitaminosis A is observed in young children if they are persistently overdosed with strong vitamin preparations. Most reported adult cases have ingested more than 100 000 i.u. daily for several months. There is probably a risk of toxic effects if more than 50 000 i.u. daily is ingested for longer periods [1].

Clinical features. There is lethargy, anorexia, weight loss and diffuse alopecia. The skin becomes pruritic, rough and dry with desquamation. The lips are dry and cracked. Follicular keratosis, patchy erythema and purpura may occur in hypervitaminosis A or due to administration of synthetic retinoids [2]. In young children, painful swellings of the limbs due to bone changes are conspicuous.Diagnosis. Vitamin A intoxication is diagnosed by consistent clinical fi ndings associated with an increased vitamin A level in the blood. Radiology may demonstrate bone changes in young children and in some adults.Treatment. No treatment is needed except immediate discontinuation of the vitamin A.CarotenodermaCarotene is the natural provitamin of vitamin A (retinol). A high intake of food containing carotene, especially carrots, causes carotenaemia (increased carotene in plasma) and may induce carotenoderma due to excess carotenes in the sweat. The condition is characterized by orange discoloration of the stratum corneum, especially on palms, soles and in areas where sebaceous glands predominate. The condition is quite harmless and subsides gradually when the dietary habits are regulated. It may occur in pregnancy as a ‘pica’. Carotenaemia is also seen in patients with hyperlipidaemia (diabetes mellitus, myxoedema) and occurs in subjects unable to convert ingested -carotene into vitamin A. Carotene traps free radicals and has been studied together with vitamin E and selenium as a possible dietary factor that may inhibit cancers [13], although this hypothesis remains unproven .Carotenoderma provides no photoprotection .Vitamin D [1,2]Vitamin D is a group of antirachitic steroid derivatives with similar biochemical activity. It is synthesized in the body as vitamin D3 (cholecalciferol), and is present in the diet from some animal sources (as vitamin D3) or from plant sources as vitamin D2 (ergocalciferol). There is little vitamin D3 in the diet although it is present in cod-liver oil, butter, eggs and liver. Vitamin D is synthesized in the skin from 7-dehydrocholesterol, which is present in abundance, by the action of 290–320-nm UV irradiation (to previtamin D) followed by a temperature-dependent conversion stage. Vitamin D2 is synthesized from its inactive provitamin, ergosterol, in plants, also by the action of UV irradiation. With adequate exposure to sunlight, dietary vitamin D is unnecessary [1]. Cholecalciferol is hydroxylated in the liver to form 25-hydroxyvitamin D, and further hydroxylation takes place in the kidney to form the biologically active 1,25-dihydroxyvitamin D [1,2]. Vitamin D2follows the same hydroxylation pathway, and is equipotent to vitamin D3. 1-Hydroxyvitamin D3 is a synthetic, highly potent vitamin D analogue used in the management of hypoparathyroidism, vitamin-D-resistant rickets and osteomalacia. Circulating vitamin D is usually measured as 25-hydroxyvitamin D, low status being defi ned as a level below 30–60 ng/L. Low levels do not refl ect the degree of exposure to solar ultraviolet light [3]. Sunbeds (tanning parlour) have been proposed as a means to increase vitamin D status. This claim is controversial since UVA does not participate in the production of vitamin D of the skin, and UVA exposure increases the risk of skin cancer and malignant melanoma [4].Vitamin D regulates calcium and phosphorus absorption and deposition, and infl uences the level of serum alkaline phosphatase. The skin is of unique importance in the synthesis, storageand release of vitamin D into the circulation [2]. Lack of vitamin D in children results in tetany and rickets (rachitis), and causes osteomalacia in adults. Elderly people produce less vitamin D3. In children, limited

exposure to sunshine may play an aetiological role; the same applies to some Asian women in the UK in whom there may be a combination of dietary defi ciency and little sunlight exposure. Regular use of sunscreens may also lead to reduced synthesis of vitamin D3 [3]. It is remarkable how exposure to sunlight a few times a week can reduce the risk of osteoporosis, osteomalacia, muscle weakness and fractures [1]. The daily needfor calciferol is 400–800 i.u. Vitamin D intoxication (long-continued administration of more than 100 000 i.u. daily) causes anorexia, vomiting, headache, diarrhoea, hypercalcaemia and hypercalciuria with osteoporosis, resembling the action of parathyroid hormone. Treatment consists of withdrawal of vitamin D, a low-calcium diet and systemiccorticosteroids. Combined calcium and vitamin D supplementation has been shown to reduce the risk of osteoporosis in people aged 50 years or older. A minimum dose of 1200 mg calcium and 800 i.u. vitamin D daily is recommended [5].Vitamin E [1,2]

Tocopherols are present in oils of vegetables, seeds, corn, whole wheat fl our, nuts and some meats; d--tocopherol is the most biologically active form. The main physiological activity of tocopherol is antioxidation. Whether the vitamin is essential to humans is still a matter of debate. In rats, guinea pigs and rabbits, a true vitamin effect has been demonstrated. Various dermatological diseases and conditions have been claimed to respond to vitamin E [1–3]. So far, no true benefi t has been defi nitely documented. Fatsoluble vitamin E is located in the stratum corneum and seems to play a role in protecting this layer from damage [2]. An inhibitory effect on hyaluronidase and a protective effect on cellular membranes and on vitamin A oxidation have been suggested, but the clinical relevance is doubtful. Neurological function in childrenwith chronic cholestasis was improved following large doses of vitamin E [4]. Large doses of vitamin E in a controlled trial have been shown to reduce the risk of myocardial infarction [5]. Vitamin E has also been used in dermatology to reduce dapsone-induced haemolysis [6] and headache [7]Vitamin B complexThe vitamins of the B complex are of great clinical signifi cancer. Isolated defi ciencies of certain B vitamins are uncommon. Mostly combined defi ciencies of the vitamins belonging to the group are involved, often occurring as a result of insuffi cient supply of protein and other essential nutrients (zinc, essential fatty acids).The vitamin B group includes:1 Aneurin (thiamine) (vitamin B1)2 Ribofl avine (vitamin B2)3 Niacin (nicotinic acid) (B3)4 Pyridoxine (vitamin B6)5 Cyanocobalamin (vitamin B12)6 Folic acid7 Pantothenic acid8 Biotin (vitamin H).AneurinSynonyms• Vitamin B1• Thiamine

Aneurin is present in yeast, cereals, liver, meat, eggs and vegetables. It functions as cocarboxylase in carbohydrate metabolism and in numerous other enzyme systems. It is involved in growth processes and in the function of the nervous system. Defi ciency results in accumulation of pyruvic and lactic acids. Dietary deficiency may be a consequence of consuming polished rice as the staple food or, more commonly, of insuffi cient nutrition associated with chronic alcoholism. Beer drinkers have a reduced risk of developing B vitamin defi ciency due to the presence of the vitamins in beer. Hypovitaminosis B1 may be associated with pregnancy, lactation, diabetes mellitus, ulcerative colitis, celiac disease, achlorhydria or myxoedema [1].Clinical features [1]. The classical form of vitamin B1 defi ciency is beriberi, characterized by anorexia, weakness, constipation, symmetrical progressive polyneuritis, cardiac insuffi ciency with oedema and wasting of musculature. The diagnosis is based on the history and a low urinary aneurin excretion following an injection of 1.0 mg of aneurin. Excretion of less than 50 g indicates a defi ciency state.Treatment. Aneurin 2–3 mg is given three times daily in mild cases. With severe cardiac and gastrointestinal involvement, polyneuritis and muscular paresis, 20 mg aneurin twice a day given parenterally is indicated.Ribofl avineSynonyms• Vitamin B2• Lactofl avineRibofl avine is a d-ribitol isoalloxazine derivative that is widely distributed in plant and animal tissues. It plays a part in intracellular redox reactions. Nutritional sources are milk and the same sources as those of vitamin B1 [1]. The human requirement is 1–2 mg daily.Clinical features. Defi ciency becomes clinically manifest after several months of deprivation due to chronic illness and malnutrition, especially in elderly women who suffer from achlorhydria, or in malnourished children with malabsorption.Aribofl avinosis may occur in alcoholic liver cirrhosis, and an association with other defi ciencies, such as pellagra, is frequent. Clinically, there is photophobia due to conjunctivitis, sometimes with corneal vascularization, angular stomatitis (perlèche) and sore lips, tongue and mouth [1]. The tongue is purplish red and smooth. A scaly seborrhoeic dermatitis-like eruption may be seen around the nose, eyes, ears and genital area (oro-oculo-genital syndrome). There is an association with zinc defi ciency as the content of the two nutrients in foodstuffs is correlated [2].Treatment. Treatment consists of 5–15 mg ribofl avine two to three times daily for 2 weeks and correction of dietary errors.PyridoxineSynonyms• Vitamin B6• PyridoxalPyridoxine is a pyridine derivative, participating as a coenzyme in transaminase and decarboxylase reactions and in the metabolism of cystein, tryptophan and essential fatty acids. It is present in many foods including yeast, eggs and various grains. The recommended daily allowance is about 2 mg. Although much is known about experimental defi ciency inmany species, the manifestations in humans are not well defi ned. Convulsions, anaemia and acrodynia may develop in infants [3]. Dermatitis has occurred and is

attributed to disturbed metabolism of unsaturated fatty acids. Pyridoxine defi ciency may follow therapy with isoniazid, hydralazine and penicillamine [4].Vitamin B12Synonyms• Cyanocobalamin• Cycobemine

Vitamin B12 is involved in nucleic acid synthesis and erythrocyte production. Defi ciency may occur in vegetarians, as plants do not contain the vitamin. Most frequently it is due to lack of the ‘intrinsic factor’ in pernicious anaemia. Hyperpigmentation, especially in dark-skinned races, may occur. It is most pronounced in skin fl exures, such as fi nger and palm creases, and on the knuckles. Pigmented streaks of the nails may be seen. An enlarged, red tongue is a characteristic fi nding [5].Folic acidFolic acid is a compound consisting of pteridine, p-aminobenzoic acid and glutamic acid. It is present in liver, meat, green leaves and milk. In the organism, folic acid is converted to folinic acid, which is the biologically active form. The conversion requires the presence of vitamin C. Folinic acid is needed for the transport of one-carbon units and plays a role in growth and erythrocyte production. The daily requirement is estimated to be about 0.4 mg. Although no consistent or specifi c cutaneous changes are related to folate defi ciency, greyish brown pigmentation on light-exposed parts has been described in megaloblastic anaemia [5,6]. Cheilitis, glossitis and mucosal erosions are common. Pigmentation similarto that of vitamin B12 defi ciency has been associated with folate defi ciency in pregnancy and during lactation. Spotty pigmentation of palms and soles and pigmented palmar creases have been described. Folate defi ciency is estimated by serum and erythrocyte folate levels. Subclinical defi ciency may be present in patients with extensive skin disease. Defi ciency causing macrocytic anaemia may result in retinal haemorrhages [7]. Synthetic folic acid may cause anaphylactic reactions [8]. The requirement for folate supplementation during methotrexate therapy is discussed in Chapters 20 and 74.NiacinSynonyms• Nicotinic acid• Vitamin B3Niacin is an essential component of two coenzymes, coenzyme I (nicotinamide adenine dinucleotide, NAD) and coenzyme II (NAD phosphate, NADP), which either donate or accept hydrogen in a wide range of biochemical reactions. Tryptophan, an essential amino acid, can be transformed to niacin, which is converted to the amide in the body. Niacin is involved in the biosynthesis of ceramides as well as of other stratum corneum lipids whichimprove the epidermal permeability layer [9].Pellagra [10]Cellular defi ciency of niacin, resulting from an inadequate dietary supply of niacin and tryptophan, is termed pellagra. In Western Europe and North America pellagra is only rarely encountered now, mostly in subjects living on an unbalanced diet, such as chronic alcoholics, and in patients with gastrointestinal diseases or severe psychiatric disturbances. Rare causes are functioning carcinoid tumours (Chapter 43) and Hartnup disease (p. 59.100). Therapy with isoniazid (which competes

biochemically with niacin owing to a close structural resemblance), 6-mercaptopurine or 5-fl uorouracil may provoke pellagra.The classical triad of clinical features is dermatitis, diarrhoea and dementia, not invariably appearing in this order. Redness and superfi cial scaling appear on areas exposed to sunlight, heat, friction or pressure. The changes resemble sunburn and subside leaving a dusky, brown-red coloration, but this occurs more slowly than typical in sunburn and exacerbation follows re-exposure to sunlight. On the face, a symmetrical ‘butterfl y’ eruption is frequently observed and there is often a characteristic well-marginated eruption on the front of the neck (‘Casal’s necklace’). Asymmetrical lesions may appear at sites of sun exposure, eczema, injury or stasis [11–12] (Figs 59.42–59.45).Gastrointestinal symptoms include pain, diarrhoea and achlorhydria in 50% of cases. In mild instances, the mental disturbance may pass unnoticed, patients perhaps being slightly depressed or apathetic. Sometimes, there may be frank disorientation, restlessness or other severe central nervous system symptoms [13]. Peripheral neuritis and myelitis are occasionally encountered.Histology. Histological examination shows hyper- and parakeratosis, acanthosis and multiple melanin granules throughout the epidermis. Such changes are suggestive, but not diagnostic, of pellagra. Drug eruptions, various forms of porphyria, photodermatitis, lupus erythematosus and actinic reticuloid may cause diagnostic diffi culty. The so-called pellagrous vulvitis, vaginitis and scrotal dermatitis may be attributed to accompanying aribofl avinosis and other defi ciencies of the vitamin B group and of zinc.Therapy. In severe cases, intravenous niacin is required in doses of 50–100 mg once or twice a day. Otherwise, oral niacin amide in a total dose of 0.5 g/day should be given. The amide is to be preferred, as it does not precipitate fl ushing, itching and burning as is seen following ingestion of niacin in large doses. Improvement can be expected within a day or two.

Kava dermopathy. Kava, a psychoactive intoxicating beverage used ceremonially and socially by Pacifi c Islanders, may produce a pellagra-like ichthyosiform dermopathy with widespread acquired ichthyosis [14,15]. Kava is produced by infusing dried roots of Piper methysticum with water or coconut milk. The cause of the skin disease has not been established; interference with tryptophan or niacin as previously suggested is not likely [15]. Interference with cholesterol metabolism akin to changes associated with lipid-lowering agents is a possibility. Kava dermopathy is curable with abstinence.BiotinSynonym• Vitamin HBiotin is a water-soluble, sulphur-containing, heterocyclic carboxylic acid involved in bacterial metabolism and possibly functioning as a coenzyme in decarboxylation and other enzymatic processes. Defi ciency can be induced by feeding raw egg-whitecontaining avidin which binds biotin and makes it poorly absorbable [16]. Short bowel syndrome in association with parenteral nutrition may cause biotin defi ciency [17,18]. Symptoms include alopecia, conjunctivitis, eczema around the nose and mouth, nail dystrophy, hyperaesthesia, paraesthesia, depression and muscle pain. A multivitamin preparation supplying 60 g of biotin daily cured an adult patient within 3 weeks [16]. Biotin seems to possess some antiseborrhoeic actions and has been used in high doses for therapy of Leiner’s disease in infants .

Inborn errors of biotin metabolism [20]. The genetically determined disorders of biotin metabolism consist of two separate diseases: holocarboxylase synthetase defi ciency and biotinidase defi ciency. Both are transmitted as an autosomal recessive trait. Holocarboxylase defi ciency (MIM #253270) presents in the neonatalperiod, affected subjects having severe symptoms of organic. acidaemia. The patients may have shown recurrent episodes of vomiting from birth and rapid respiration as a sign of severe metabolic acidosis. There are seizures, hypo- as well as hypertonia, electroencephalogram abnormalities, and the disease progresses to death unless diagnosis and effective therapy supervene. An erythematous, scaly rash is prominent over most of the body in the patients who survive the fi rst days of life. The skin lesions may resemble ichthyosis and seborrhoeic dermatitis. The pattern of excretion of organic acids is characteristic, especially 3-hydroxyisovaleric acid and 3-methylcrotonylglycine in urine being increased. Lactic acidaemia is striking. The molecular defect is in the enzyme holocarboxylase synthetase. Biotinidase defi ciency (multiple decarboxylase defi ciency, MIM #253260) usually presents after 3 months of age. The cutaneous lesions may resemble those of acrodermatitis enteropathica, that is severe zinc defi ciency, with periorifi cial eczematous rash on theface, nail dystrophy (onychoschizia) and skin infection. The hair is sparse, and there may be total alopecia. Neurological symptoms are prominent with myoclonic seizures, ataxia, lethargy and developmental delay [21]. There are low levels of biotin in blood and urine. The fundamental defect is in biotinidase, which normally acts on biocytin, a biotin–lysine complex, thereby separating biotin from lysine [19].Biotin treatment. Both of the biotin-related disorders discussed above are treated with an oral dose of biotin, usually 10 mg/day but some patients need less and some have required as much as 40 mg/day. Uncombable hair syndrome may respond to a low oral dose of biotin [22].

Vitamin C [1–3]Synonym• Ascorbic acidVitamin C is a relatively strong organic acid, chemically related to the carbohydrates. Only the laevo form is biologically active. Ascorbic acid is a strong reducing agent, easily oxidized to dehydroascorbic acid, with which it constitutes a reversible redox system. Vitamin C plays a central role in collagen and groundsubstance formation, metabolism of aromatic amino acids (phenylalanine, tyrosine), reduction of folic acid to folinic acid and a broad range of biochemical redox reactions, including the preservation of sulphur-containing enzymes in a reduced form. It occurs naturally in cabbage, potatoes, green vegetables and fruits. The recommended daily dose is 30–80 mg; a daily intake of 10 mgprevents scurvy.Vitamin C defi ciencySynonyms• Scurvy• Scorbutus• Hypovitaminosis CUnlike most other animals, humans and guinea pigs are unable to synthesize ascorbic acid due to lack of the enzymatic pathways for synthesis of l-ascorbic acid from d-glucuronic acid. In the defi ciency state, collagen and ground-substance

synthesis are depressed, which leads to a multiplicity of symptoms involving bones, mucous membranes and skin.Aetiology. Lack of vitamin C is still a serious problem in many parts of the world where access to fruit and vegetables is limited and where general malnutrition prevails. By contrast, most cases in developed countries are a consequence of food faddism, ignorance or alcoholism [4,5]. Danish beer no longer contains vitamin C as an antioxidant, and can therefore no longer prevent scurvy in alcoholics [6]. Malnourished children with scurvy (Barlow’s disease) [7] may still be a paediatric problem [8] and vitamin C defi ciency has been observed in teenagers living on processed food devoid of fresh fruit and vegetables [9]. In patients with chronic gastrointestinal disturbances, subclinical scurvy may be present. Elderly men living alone, who rarely get fresh fruit or vegetables and who may abuse alcohol, are particularly at risk. Scurvy may be a presenting sign of undiagnosed psychiatric illness [10], and may appear with ecchymosis, perifollicular petecchiae and haemorrhagic pustules on a previously injured extremity The cause of scurvy observed in liver transplant patients is notclear [12].Clinical features [4]. (Figs 59.46 and 59.47). The initial skin change is follicular keratosis with coiled hairs on the upper arms, back, buttocks and lower extremities. Later, perifollicular haemorrhage with blood pigment discoloration especially on the legs, swollen bleeding gums, stomatitis and epistaxis occur. Large skin haemorrhages may be seen. Anaemia is usually present, and the patient appears resentful and mentally depressed. In the infant, dental development is impaired and oral changes may be severe. Tender subperiostal haematomas may develop and dominate the picture. Chronic hypovitaminosis C with ‘woody’ oedema and discoloration of the legs as the presenting feature has been described.Subnormal serum levels of vitamin C are present (normal range about 17–94 mol/L). The signifi cance of low values without clinical symptoms is doubtful.Treatment. The scorbutic patient should be treated with oral vitamin C 100 mg three times daily in addition to protein-rich food [4]. The response is dramatic. It is advisable to continue the therapy for several weeks to ensure repletion of the emptied body stores.

Vit. C is available in the market as a variety of creams, serum and transdermal patches. Of these, only the serum contains active Vit. C in an almost colorless form. It is unstable and, on exposure to light, gets oxidized to Dehydro Ascorbic Acid (DHAA), which imparts a yellow color. The stability of Vit. C is controlled by maintaining a pH of less than 3.5. At this pH, the ionic charge on the molecule is removed and it is transported well across the stratum corneum.[3,5,9]

From a clinical point of view, it is important to note that the efficacy of the Vit. C serum is proportional to the concentration, but only up to 20%.[3] The half-life in the skin after achieving maximum concentration is 4 days. A persistent reservoir of Vit. C is important for adequate photoprotection, and can be achieved by regular 8-hourly applications.[1,5] As UV light lowers tissue Vit. C levels, topical Vit. C is best used after exposure to UV light and not prior.[1–3] A combination of tyrosine, zinc and Vit. C has been shown to increase the bioavailability of Vit. C 20-times vis-à-vis using just Vit. C.[2]

A variety of creams with Vit. C derivatives are available in the market. As a dermatologist, it is important to know that not all preparations are physiologically effective. Some are not delivered into the dermis in an adequate quantity, while others do not chemically convert to the biologically active form of Vit. C in the skin.[1,2,4]

Magnesium ascorbyl phosphate (MAP) is the most stable and preferred ascorbyl ester. This lipophilic molecule is easily absorbed into the skin, and the rate-limiting step for absorption is its release from the vehicle, and not the rate of diffusion across the stratum corneum as one might suppose. MAP has a hydrating effect on the skin and decreases transepidermal water loss. It is also a free radical scavenger that is photoprotective and increases collagen production under laboratory test conditions.[1,3] Other useful stable esterified derivatives are:

1. Ascorbyl 6 palmitate, a lipophilic free radical scavenger that hydrolyses to Vit. C and palmitic

acid.[3,8]

2. Disodium isostearyl 2-0 L-ascorbyl phosphate (VCP-IS-Na), another reliable and popular

derivative of Vit. C with a C8 alkyl chain attached to the stable ascorbyl moiety. This ensures

increased permeability across the epidermis

3. Ascorbic acid sulfate.[1]

4. Tetraisopalmitoyl ascorbic acid, a lipophilic provitamin and sodium ascorbate, are derivatives

under research.

Vitamin A, B1, B2, B6, B12, biotin, nicotinic acid, panthotenic acid, vitamin C, E and K have been used for various skin disorders. The use is mostly based on the similarity of the skin manifestations seen in their deficiencies, except for the rare cases of clear deficiency like pellagra. Recent introduction of vitamin A and D analogues for psoriasis and keratinization disorders resulted in significant progress in clinical dermatology. Application of vitamin C, E and beta-carotene++ for UV-induced skin damages are being studied, and the vitamins will be more important in dermatology in the future.

As Vit. C is hydrophilic, there is a marked interest to find methods of efficient transepidermal delivery of the stable active compound. If antioxidants could be delivered in high concentration through the stratum corneum barrier, then a dermal reservoir of protective antioxidant could be increased and thus photoprotection would be enhanced.[5] As stated earlier, the use of stable lipophilic esterified derivatives of Vit. C is being explored for the purpose.[5,8,10–13] Extensive research is underway to investigate microspheres, nanoparticles and

multilayered microemulsions for graded topical delivery. Trials have been performed with Vit. C and Vit. E in the same multilayered emulsions together.[6] Both electroporation and iontophoresis have been used to enhance penetration of Vit. C into the dermis.[11,14,15] Application of Vit. C to the treated skin surface after microdermabrasion and CO2 or Er-Yag resurfacing increases the transepidermal penetration of Vit. C 20-times.[2,16] It has also been observed that Vit. C is a good priming agent and a post-operative agent for the prevention of erythema following laser resurfacing. Smokers have been found to have low Vit. C levels in the dermis, akin to UV-damaged skin. Smoking-related skin ageing is another area where efficacy of Vit. C is being explored. Another very useful application of Vit. C may be striae, where a study has shown that daily application of Vit. C combined with 20% glycolic acid over 3 months can significantly improve striae.