Psoriasis skin vitamin

Calcipotriol is a vitamin D derivative used topically for psoriasis. It does not cause skin discoloration and does not stain clothes. 

Phototherapy is the generic term covering therapies which use light either with or without a sensitiser. Those that do not require a sensitiser use the natural chromophores within the tissue to perform this function e.g. treatment of vitamin D deficiency in rickets, and neonatal jaundice). Those that do use an added sensitiser include photochemotherapy (largely psoriasis and skin disorders) and photodynamic therapy (currently mainly cancer). Photodynamic therapy is differentiated from photochemotherapy by its additional requirement for the presence of oxygen at molecular or ambient levels.In this text we will deal only with photodynamic therapy since, at the present time, this is the main driving force in phototherapy. ° ... 

Posner and coworkers have prepared a series of semi-synthetic and synthetic ether and ester-linked dimers that were found to have potent anti-proliferative and antitumour activities in vitro. Some of these trioxane dimers were found to be as antiproliferative as calcitriol, the hormonally active form of vitamin D, which is used to treat psoriasis, a skin disorder characterized by uncontrolled cell prohferation. Of the semi synthetic dimers, a polyethylene glycol-linked dimer 107, with S-stereochemistry at both of the lactol acetal positions, was found to be very anti-proliferative and showed activity against leukaemia and colon cancer cell hues in the National Cancer Institute (NCI), USA 60-cell line assay. 

Calcipotriol is a vitamin D3 derivative which is used as a topical agent in the treatment of psoriasis. Although not completely elucidated its mechanism of action seems to be based on inhibition of the proliferation and stimulation of the differentiation of epidermal keratinocytes. Adverse effects include irritation of the skin but also urticarial reactions. Calcipotriol has 100 fold less vitamin D activity as its active vitamin D3 metabolite calcitriol. However, calcipotriol in overdose can cause symptoms of hypercalcemia. 

Calcipotriene (Dovonex), a synthetic vitamin D3 derivative, is indicated for the treatment of moderate plaque psoriasis. Its mechanism of action is unknown, although it competes for calcitriol receptors on keratinocytes and normalizes differentiation. It also has a variety of immunomodulatory effects in the skin. Although the drug can cause local irritation, the most serious toxicities are hypercalciuria and hypercalcemia, which are usually reversible. 

Mechanism of Action A synthetic vitamin Dj analog that regulates skin cell (kerat-inocyte) production and development. Therapeutic Effect Preventing abnormal growth and production of psoriasis (abnormal kerafinocyte growth). Pharmacokinetics Minimal absorption through intact skin. Metabolized in liver. 

The past twenty years have witnessed considerable progress in the synthesis and use of other retinoid-like molecules related to vitamin A. The aromatic retinoid etretin (8.54) and its ester etretinate (8.55) had some effectiveness in the treatment of psoriasis, a disorder of skin. 13-cA-Retinoic acid (isotretinoin) produces sebaceous gland atrophy and could prove useful in the treatment of severe acne vulgaris. Although these compounds have toxic side effects and are not in regular use, they have opened up new therapeutic possibilities. Retinoic acid (tretinoin, 8.56) has been employed in the treatment of acne. 

Vitamin A may be helpful in certain diseases of the skin, such as acne, psoriasis, Darier s disease, and ichthyosis. 

The stratum corneum consists of denucleated corneocytes filled with cross-linked proteins, while the intercellular space is occupied by lipids synthesized prior to and during cornification [24], Formation of this barrier relies on the cornification of epidermal keratinocytes, which undergo growth arrest, terminal differentiation, and an epidermal-specific cell death, referred to as planned cell death [25], Abnormalities in any of these programmed events may lead to epidermal disorders such as psoriasis, atopic dermatitis, and cancer. Flowever, biological events that enable basal cells (stem cells) to proliferate, differentiate, and commit planned cell death are still poorly understood [10]. The keratinocyte differentiation process can be stimulated by prodifferentiation agents such as extracellular calcium and 1,25-dihydroxy cholecalciferol (referred to as vitamin D3 hereafter) [23], Aberrant or absent differentiation can be found in other skin disorders such as atopic keratosis, seborrheic keratosis, and rosacea. 

For dermatological treatment the main focus has been on vitamins A and D. Retinoids have been used systemically and topically for the treatment of acne and a variety of hyperkeratotic disorders including psoriasis, ichthyoses, and lichenoid dermatoses as well as skin cancer.1 Vitamin D-analogs are of great importance for the topical treatment in psoriasis. 

In reconstructed human epidermis the presence of vitamin C was required to normalize stratum corneum lipids, which was accompanied by an improvement of skin barrier formation.36 Interestingly the ascorbic acid concentration in the skin of atopic dermatitis37 and psoriatic patients38 measured in vivo by microdialysis was significantly lower than in healthy subjects. In psoriasis there was no significant difference in lesional versus nonlesional skin. There has also been demonstrated a decrease of ascorbic acid concentration in skin with increasing age.39... 

Topical vitamin D analogs as calcipotriol, and tacalcitol are well established, effective and safe preparations for the treatment of psoriasis vulgaris due to their antiproliferative and prodifferentiating effects on keratinocytes.110 They can be used either as monotherapy or in combination with other treatment modalities.111 The main side effect is the increasing risk ofhypercalcaemia with increasing amounts of vitamin D analogs applied to the skin. 

During the 1980s, two drugs used to treat different types of skin diseases were found to be teratogenic. The drugs, generic names are isotretoin and etretinate, respectively, and they are synthetic retinoids (i.e., derivatives of vitamin A). Isotretoin (Accutane) was prescribed for the treatment of acne while etretinate was prescribed for psoriasis. 

The first line of treatment is usually the application of topical products, ranging from over-the-counter products to topical steroids. Emollients may be used to reduce dryness and scaling, as well as reducing the hyperproliferation associated with plaque psoriasis. The use of vitamin D analogues, tazarotene, dithranol or coal tar preparations aims to lessen or remove the patient s scaly plaques. However, excess use can irritate the skin and their use is not recommended for the more irritant forms of psoriasis. Tar baths and tar shampoos (containing coal tar) may help with managing the condition. Treatment, if nonirritating, should be continued for 4-6 weeks and thereafter assessed. Emollients... 

Vitamin D has recently found an association with psoriasis, a common disease of the skin. Psoriasis is not curable, but a variety of skin ointments can reduce the severity of the skin lesions. One of these ointments is a chemical analogue of vitamin D called calcipotrlene. Calcipotrienc was developed after initial observations that oral or topical caldtriol was effective against the disease, The drug results in improvement tn 60% of patients (Greaves and Weinstein, 1995),... 

Unfortunately, careful studies have shown that fish oils do not have this effect (Soyland et it ., 1993). Psoriasis patients might find comfort with the recent demonstration that vitamin D-based compounds, when applied to the skin, can result in a remarkable decline in skin lesions. 

More promising have been recent attempts to show a difference by the response of the skin to injury. Reid (R3) and Reid and Jarrett (R4) have shown an increased erythema response of normal-appearing skin of psoriasis patients to applications of vitamin A with increased release of acid phosphatase in the uninvolved but psoriatic epidermis. Braun-Falco et al. (B32) found an increased number of cells incorporating tritiated thymidine after Scotch tape stripping. While Hell and Hodgson (H13) noted increased uptake of thymidine in vitro by uninvolved skin of psoriatic subjects. There may in the future be a way of reliably... 

Calcipotriene is an antipsoriatic agent. It is a synthetic vitamin Dj analog. In a manner similar to vitamin D, calcipotriene regulates skin cell production and development, thereby modifying the abnormal growth and production of kerati-nocytes, responsible for the scaly red patches characteristic of psoriasis (see Figure 105). Calcipotriene is indicated in the treatment of plaque psoriasis. Scalp solution topical treatment of chronic, moderately severe psoriasis of the scalp. 

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