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Topical Vitamin D Analogues

Three vitamin D analogues are available in the UK for topical treatment of psoriasis, namely calcipotriol, calcitriol and tacalcitol.

Calcipotriol

Calcipotriol is available in ointment and cream formulations containing calcipotriol at the concentration of 50 microg/g, and as a scalp lotion (50 microg/ml). Treatment may be used once or twice daily. Improvement usually becomes apparent within 2 weeks, and continues for at least 8 weeks, at which point some patients are clear but the majority reach a plateau. In the latter case, the improvement can often be maintained by continuing treatment. Calcipotriol is safe, provided that the manufacturer's recommendations are followed and the maximum dose 100g/week for adults, 75g for children over 12 and 50g for children of 6-12 years is not exceeded. Use in children under 6 is not recommended. Calcipotriol is more convenient to use than tar or dithranol and does not produce the side effects of topical corticosteroids However, self limiting, irritant reactions are common.. Calcipotriol has become one of the first-line treatments for psoriasis vulgaris.

Efficacy

Calcipotriol is an effective treatment for mild to moderate chronic plaque psoriasis, more so than calcitriol, tacalcitol, coal tar, and short contact dithranol. Only potent topical corticosteroids seem to have comparable efficacy at eight weeks. Although calcipotriol causes more skin irritation than topical corticosteroids this has to be balanced against the potential long term effects of corticosteroids. Skin irritation rarely led to withdrawal of calcipotriol treatment.

Use in pregnancy: Although calcipotriol is not believed to be teratogenic, there is little experience of its use in pregnancy.

Safety and side effects

Calcipotriol is irritant and may give rise to redness, soreness or pruritus in around 20% of patients during 6 weeks of treatment. Such reactions are particularly common when the face is inadvertently contaminated with medication. This is self-limiting but occasionally necessitates a break in treatment. This irritancy largely precludes the use of calcipotriol on the face. Flexures are also vulnerable. The maximum recommended rate of usage is 100g of ointment weekly. This should not be exceeded, as there is a risk of vitamin D intoxication.

When doses below 100g weekly have been used, no evidence of any effect has been observed. However, at 100g weekly a small increase in urine calcium excretion is detectable. When the dose rate is increased to 200g or 300g weekly, both urine and serum calcium levels rise, and serum parathyroid hormone is depressed. There are now a number of reports of individual patients in whom hypercalcaemia has developed when the maximum recommended dose rate has been exceeded. Absorption of the vitamin D analogue may be higher in erythrodermic psoriasis, and hypercalcaemia has been reported in such a case when 200g of ointment were applied in 7 days. In another erythrodermic patient, hypercalcaemia developed when using 100g of ointment weekly, and recurred when the treatment was reintroduced at a lower dose rate. There have been four reports of probable sensitisation to calcipotriol. Experience has not lead to concern over the risk of psoriasis rebounding after topical calcipotriol, in a manner similar to that said to occur with topical corticosteroids.

Patient acceptability

Calcipotriol is an improvement on previously existing topical treatments for psoriasis, except for those patients who use emollients alone. Compared to dithranol, it is less irritant, less messy and more convenient. Patients' opinions regarding the acceptability of these treatments have been directly compared in a large trial: calcipotriol was considered more acceptable. It is less messy than tar, and is free from the odour of tar, which some patients dislike. Calcipotriol is free from the side effects of topical corticosteroids, which are a source of concern to patients. Calcipotriol is often irritant. Although this is a disadvantage, it is only occasionally necessary for treatment to be discontinued as a result.

Synergy with other treatments

Published data suggest that there is a useful additive effect when calcipotriol is used in conjunction with PUVA, cyclosporin, and UVB. It would appear possible that the use of calcipotriol may allow a useful dose sparing effect with UVB phototherapy or PUVA, and systemic treatments, and thus reduce their toxicity, but more research is required to address this question.

References

Mason J, Mason AR, Cork MJ. Topical preparations for the treatment of psoriasis: a systematic review. Br J Dermatol. 2002 Mar;146(3):351-64.

Calcitriol 

This ointment contains vitamin D in the form of 1:25 dihydroxy-cholecalciferol, at the concentration of 3 microg/g. Advantages of calcitriol are that it is less irritant than calcipotriol and may, therefore, be suitable for use on the face and flexures. Duration of remission is greater than with potent topical steroids. The rate of application should not exceed 30g ointment per day and it should not be applied to more than 35% of the body surface daily. More published data are currently needed, before clear guidelines can be issued to establish the precise role of this product. It is a clean non-smelly preparation which is well tolerated and more effective than short contact dithranol therapy.

Use in pregnancy and children

Calcitriol has not been licensed in children and not adequately assessed in pregnancy. There is some evidence in animals of developmental toxicity at doses, which caused maternal toxicity, and calcium levels should be monitored in situations where it has been used in restricted amounts out of necessity. It also passes into breast milk and should be avoided in breastfeeding. 

Tacalcitol

Tacalcitol 4 microg/g is also less irritant but less effective than calcipotriol. It is suitable for use on the face and flexures and the amount applied should not exceed 10g/day. It has not been licensed for use in children and although no toxicity has been found there is insufficient data to support its use in pregnancy and lactation.

Calcipotriol/betamethasone dipropionate

A novel ointment comprising betamethasone 0.05% (as dipropionate), calcipotriol 50 micrograms/g has greater efficacy than either constituent used alone. However, the cost of treatment is also greater and the restrictions that apply to potent topical steroids in psoriasis (see below) apply.

It is normally used in the initial treatment of stable plaque psoriasis where calcipotriol has failed. Patients should be instructed to apply once daily to a maximum of 30% of body surface for a maximum of 4 consecutive weeks; max 15 g daily, max 100 g weekly.  After this period repeated treatment with Dovobet can be initiated under medical supervision. A frequent compromise is to use the combined product for 4 weeks alternating with 4 week periods of Calcipotriol.  Over the 52 weeks this alternating combination optimised response with the least side effects. It is not recommended for children and adolescents under 18 years and is unsuitable for use on the face or flexures.

Potent topical corticosteroids should be avoided or given only under specialist supervision in psoriasis because, although they may suppress the psoriasis in the short term, relapse or vigorous rebound occurs on withdrawal (sometimes precipitating severe pustular psoriasis). Topical use of potent corticosteroids on widespread psoriasis can lead to systemic as well as to local side-effects.

Tazarotene 

Tazarotene (0.05% and 0.1%) gel is a topical retinoid which is effective in psoriasis. It is clean and odourless and should be appled once daily for 12 weeks. Irritation is common but it is minimised by adjusting the strength of the treatment and by applying tazarotene sparingly to the plaques, avoiding normal skin. It is suitable for the treatment of moderate plaque psoriasis affecting up to 10% of skin area. Patients should be instructed to wash their hands immediately after use, avoid contact with eyes, face, skin folds, hair-covered areas of the scalp, and eczematous areas. They should also avoid excessive exposure to UV light (including sunlight, solariums, PUVA or UVB treatment) and should avoid applying emollients or cosmetics to the treated area within 1 hour of application.

Use in pregnancy and children

As a retinoid this preparation is potentially teratogenic and should strictly be avoided in pregnancy. Women of child-bearing age must ensure adequate contraceptive protection. It is not recommended for use in breastfeeding mothers or children/adolescents under the age of 18.

Side effects include local irritation (more common with higher concentration and may require discontinuation), pruritus, burning, erythema, desquamation, non-specific rash, contact dermatitis, and worsening of psoriasis; rarely stinging and inflamed, dry or painful skin.

This information forms part of the current BAD guidance document for the general management of psoriasis.  Other sections in the document comprise: