Vitamin D analogues Vitamin D3 is naturally synthesised in the epidermis. The mechanism involves natural UVB falling on the skin and converting 7- dehydrocholesterol into vitamin D which then binds with vitamin D binding protein. In this form, the vitamin D is transported around the body to the liver and kidneys where it undergoes a number of hydroxylations (addition of oxygen and hydrogen molecules) before becoming the active substance 1,25-dihydroxyvitamin D3, otherwise known as calcitriol. Receptors for the action of calcitriol can be found in human epidermis and also in melanocytes, Langerhans cells, fibroblasts, endothelial cells, T-lymphocytes, macrophages and granulocytes (Camisa, 2004c). Calcitriol has been shown to inhibit cell proliferation and induce terminal differentiation within the epidermis. It also affects calcium homeostasis by stimulating the absorption of both calcium and phosphate through the small intestine and by promoting mineralisation and osteolysis in the bones. The synthetic vitamin D analogues (calcipotriol, tacalcitol and calcitriol) work in the same way as naturally occurring calcitriol, inhibiting cell proliferation and encouraging the skin cells to mature normally. Calcipotriol is more effective than tacalcitol and calcitriol (Ashcroft et al., 2000) and less calciotrophic (i.e. less likely to impact on calcium levels) than calcitriol. The systematic review undertaken in 2000 showed that calcipotriol was more effective than coal tar, combined coal tar 5%, allatonin 2% and hydrocortisone 0.5% and short-contact dithranol. When measured at 6 weeks it was more effective than potent topical steroids, although this effect was reversed by 8 weeks (Ashcroft et al., 2000). Interestingly in a further study carried out in The Netherlands where calcipotriol treatment was compared with short-contact dithranol treatment in a day-care setting, dithranol treatment was seen as more effective (van de Kerkhof et al., 2006). Thus, where skilled staff are available within a day-care setting, the use of dithranol could be considered as a first line treatment. Its efficacy is significant; however, as is described later in this section, its application and potential side effects are considerable which can make its use outside a clinical setting, undesirable. Method of application Vitamin D analogues are designed for use in stable CPP. In practical terms, the vitamin D analogues are relatively easy to apply. They are odourless and come in cream or ointment formulations, so the most appropriate type of product can be selected. Amounts and contraindications are outlined in Table 8.2. Each brand of vitamin D analogue recommends a different quantity per application. Where the manufacturer makes a specific recommendation it is quoted in Table 8.2. The cream or ointment should be applied to the plaque and rubbed in gently; however, if any is left on the skin, clothing should not be worn straight away as this may rub off the product. Side effects include slight stinging or irritation on application which should resolve shortly after application. If calcitriol or calcipotriol get onto sensitive skin, for example the face, they may cause more severe irritation and erythema. However, tacalcitol can be used on the face and in flexures. It is important that patients are instructed to wash their hands after application of the product so that they do not inadvertently get it onto more sensitive skin.
Calcipotriol is also available as a scalp application. It is in a liquid form which is useful for treating psoriasis once the scale has been removed. Table 8.3 outlines how scalp treatments should be applied.
The patient should be warned that it may take up to 4 weeks to see any positive impact of the treatment, that this is normal and that they should persevere. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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