K.C. Smith, MD, FRCPCa and M. Lebwohl, MDb
aNiagara Falls, Ontario, Canada, bMt. Sinai Medical Center, New York, New York, USA
Topical corticosteroids are important in psoriasis therapy. However, there are other worthwhile options available including tar, anthralin, tazarotene, calcipotriol, topical PUVA, and topical porphyrin derivatives. With growing public reluctance to use systemic medications, topical treatments for psoriasis could become increasingly important in the future.
Key Words: anthralin, calcipotriol, corticosteroids, psoriasis, PUVA, tar, tazarotene
There have been advances in psoriasis therapy, but topical corticosteroids remain an important part of the treatment program. These drugs are useful not only to control this disease, but also to limit the irritation caused by medications such as tazarotene and anthralin. Ultrapotent topical corticosteroids can also be valuable for reducing the discomfort of acute UV light burns, a complication of UV light treatment1.
Anthralin penetrates preferentially into the abnormal stratum corneum of psoriatic lesions after short exposure (e.g., 30 minutes), sparing the adjacent normal skin. This facilitates “short contact” anthralin therapy6. The major side effects of anthralin therapy, (i.e., erythema, skin irritation and staining of skin and clothing) can be reduced7. Patients should be instructed to wash anthralin cream off with cool water and no soap, because hot water and soap will liberate this drug from the liposomes in the cream, resulting in staining and irritation to normal skin.
Suggested mechanisms of action for anthralin include:
- generation of free radicals
- inhibition of DNA synthesis
- alteration of the epidermal growth factor receptor pathway
- alteration in mitochondrial respiratory function8
Tazarotene gel is a retinoid that is rapidly converted in the skin to its active metabolite tazarotenic acid. This acid then selectively binds to the gamma and beta retinoic acid receptors that moderate the abnormal keratinocyte differentiation and hyperproliferation, as well as the increased inflammation associated with psoriasis. The onset of action is slower than with topical corticosteroids, but tazarotene, in some cases, can induce several months of remission, during which no treatment is needed9. Patients using tazarotene must be carefully instructed in the correct use of this medication, with particular emphasis on applying tazarotene only to thick scaly areas, and discontinuing tazarotene once the skin has become flat and nonscaly. We recommend the application of an appropriate mid potency corticosteroid later in the day for reducing irritation from the tazarotene, and speeding up resolution of the psoriasis.
Tazarotene is usually very well tolerated on the scalp, perhaps because of the numerous sebaceous glands on the scalp that help to reduce the dryness. Dryness can be a problem when tazarotene is applied to other parts of the body.
|Drug||Therapy (mono or combined)||Side effects||Course of disease|
|Anthralin||Ointment – mono||Sensitivity, irritation, allergy, rash||Chronic treatment|
Can induce long remissions
|Tazarotene||Monotherapy or used with corticosteroids or UVB||Retinoid reaction||Sometimes in remission for months|
|Calcipotriol||Used with UVB or with adrenocorticosteroids||Dermatitis, flare of psoriasis||Chronic treatment|
|Corticosteroids||Monotherapy–intermittent or combined with all other treatments||Skin atrophy, telangiectasis, rare systemic effects||Chronic treatment Rebound effect when treatment is discontinued|
|Crude coal tar||Used with salicylic acid or sulfur||Stings, stinks, stains, photosensitive||Chronic treatment|
Table 1 – Current psoriasis treatments.
*Urea is preferred. It works just as well, and won’t degrade calcipotriol.
Calcipotriol* – Calcipotriene**
Calcipotriol (Dovonex, Daivonex) is an analogue of vitamin D that has minimal effects on system calcium metabolism. It is available as cream, ointment and lotion, and its antipsoriatic effect is likely mediated by inhibition of keratinocyte differentiation/proliferation, and by inhibition of T-lymphocyte activation10. Calcipotriol is usually well tolerated, but can occasionally cause irritation, especially if applied to the face or genital area. To reduce the risk of hypercalcemia the total amount applied should be less than 100gm per week. Tachyphylaxis to calcipotriol has not been observed, and this drug is safe for long-term use.
Salicylic acid instantly degrades calcipotriol. Therefore, when extemporaneous compounds are formulated, it is important to avoid using topical salicylic acid preparations at the same time as calcipotriol. Urea, however, does not cause degradation of calcipotriol3.
|Drugs||Plaque psoriasis||Nail psoriasis||Scalp psoriasis|
|Cacipotriol||Yes||Yes – when mixed with 10% urea||Yes|
|Crude Coal Tar||Yes||No||Yes|
Table 2 – Site treatment recommendations.
To reduce the total amount of topical corticosteroids required for psoriasis control, patients are often advised to use noncorticosteroid therapies. These can include other topical medications, UV light treatment, and systemic medications like methotrexate, acitretin (Soriatane), or cyclosporine (Neoral). Conversely, patients taking these treatments are often well advised to continue with topical corticosteroids, thus reducing the amount of systemic medication and the UV light required to control their psoriasis.
An increasing number of physicians are prescribing the twice weekly application of ultrapotent topical corticosteroids like halobetasol propionate (Ultravate), betamethasone dipropionate–augmented (Diprolene), clobetasol propionate (Dermovate, Temovate), and diflorasone diacetate (Psoracom) to reduce the risk of tachyphylaxis and skin atrophy. Another approach is to use newer topical corticosteroids like mometasone furoate (Elocom, Elocon) or fluticasone propionate (Cutivate), which may have an improved ratio of anti-inflammatory effect to atrophogenic potential.
Occasionally for use on thick plaques of psoriasis, penetration enhancing agents like salicylic acid or urea are added to topical corticosteroids. Examples of such products include betamethasone dipropionate 0.05%/salicylic acid 2% (Diprosalic ointment and lotion), and diflucortolone 21-valerate 0.1%/salicylic acid 3% (Nerisalic oily cream). Salicylic acid and urea weaken the hydrogen bonds in keratin, and facilitate penetration of the corticosteroid through the keratin to the dermis2. Salicylic acid also blocks UVB light. Patients taking UVB light treatment must apply these preparations consistently or they could increase their risk of under- or overexposure to the UVB therapy4.
Tar stings, tar stinks, and tar stains! There is little objective evidence demonstrating that adding tar to a topical corticosteroid adds value. Tar increases costs while reducing the shelf life and cosmetic acceptability of the product. Tar is nonstandard, containing about 10,000 different chemicals, and can be highly variable from batch to batch. In addition, tar can cause photosensitivity. Tar has been used in the past as an adjunct to phototherapy (e.g., Goeckerman treatment). It has been largely displaced in recent years by more predictable and better tolerated topical and systemic agents5.
Psoralen plus UVA light treatment can be administered topically as “bath PUVA”. This can be very effective, but there is increased risk of phototoxicity and the topical application of psoralen is much more inconvenient than the systemic use of this medication.
Topical porphyrin derivatives
Light-activated porphyrin derivatives for topical and systemic use in psoriasis and other dermatologic conditions are under development11.
With growing public reluctance to use systemic medications we can expect topical treatments for psoriasis and other skin conditions to become increasingly important in the future. This trend will be supported by our growing understanding of the pharmacology and physical chemistry of topical medications, of skin physiology and cell biology, and of the psychological and compliance issues which influence the acceptability of various treatment modalities.
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- Personal communication, Dr. Brian Schwartz, Leo Pharma, circa 1995.
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- Weinstein GD, Krueger GG, Lowe NJ, et al. Tazarotene gel, a new retinoid, for topical therapy of psoriasis: vehicle-controlled study of safety, efficacy, and duration of therapeutic effect. J Am Acad Dermatol 37(1):85-92 (1997 Jul).
- Reichrath J, Muller SM, Kerber A, Baum HP, Bahmer FA. Biologic effects of topical calcipotriol (MC 903) treatment in psoriatic skin. J Am Acad Dermatol 36(1):19-28 (1997 Jan).
- Lui H. Photodynamic therapy in dermatology with porfimer sodium and benzoporphyrin derivative: an update. Semin Oncol 21(6 Suppl 15):11-4 (1994 Dec).