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Topical therapies for Evidence-based review Tarek Afi fi , MD Gillian de Gannes, MD, CCFP Changzheng Huang, MD Youwen Zhou, MD, PHD, FRCPC

ABSTRACT OBJECTIVE To review current understandings of and approaches to topical psoriasis therapies and to assess their effi cacies and adverse eff ects. QUALITY OF EVIDENCE Literature from 1987 to 2003, inclusive, was reviewed via MEDLINE using the search term “psoriasis” combined with “topical treatment.” Articles were prioritized based on their level of evidence, favouring double-blind, randomized controlled trials over other comparison studies. Other studies were included where level I research was unavailable. No level III research was included. MAIN MESSAGE Psoriasis is very common and causes substantial morbidity. Because most psoriasis is mild to moderate, patients are well suited to outpatient topical therapy. Advances in topical treatments for psoriasis have kept pace with a rapidly evolving comprehension of its pathogenesis, making a review of current therapies useful for those who treat psoriasis. While research supports continued reliance on as fi rst-line therapy, comparable effi cacy has been shown for D analogues and topical , albeit with a slight increase in adverse eff ects. CONCLUSION The combination of and analogues or topical retinoids is perhaps the most promising current treatment. It seems to have increased effi cacy and fewer side eff ects.

RÉSUMÉ OBJECTIF Faire le point sur ce que l’on sait des diff érentes formes de traitement topique du psoriasis et évaluer leur effi cacité et leurs eff ets indésirables. QUALITÉ DES PREUVES Une recherche a été eff ectuée dans MEDLINE de 1987 à 2003 inclusivement à l’aide des mots-clés « psoriasis » et « topical treatment » combinés. On a classé les articles repérés selon leur niveau de preuve, en favorisant les essais randomisés à double insu plutôt que les essais comparatifs. D’autres études ont été retenues lorsqu’il n’y avait pas de recherche de niveau I. Les recherches de niveau III ont été exclues. PRINCIPAL MESSAGE Le psoriasis est très fréquent et c’est une importante cause de morbidité. Comme la plupart des cas sont bénins ou modérés, les patients peuvent généralement bénéfi cier d’un traitement topique en externe. Le traitement topique du psoriasis a connu des progrès rapides parallèlement à l’amélioration des connaissances sur la pathogenèse du psoriasis, si bien qu’il est opportun de faire le point sur les modalités thérapeutiques actuelles. Même si les données actuelles préconisent toujours les corticostéroïdes comme traitement de première ligne, on a observé que les analogues de la vitamine D et les rétinoïdes topiques ont une effi cacité comparable, quoiqu’ils aient un peu plus d’eff ets indésirables. CONCLUSION La combinaison de stéroïdes et d’analogues de la vitamine D ou de rétinoïdes topiques semble être le traitement le plus prometteur actuellement. Il semble avoir une effi cacité accrue et moins d’eff ets secondaires.

This article has been peer reviewed. Cet article a fait l’objet d’une évaluation externe. Can Fam Physician 2005;51:519-525.

➛ FOR PRESCRIBING INFORMATION SEE PAGE 568 VOL 5: APRIL • AVRIL 2005 d Canadian Family Physician • Le Médecin de famille canadien 519 CME Topical therapies for psoriasis

soriasis is a psychosocially, and at times med- Pathogenesis ically, debilitating disorder that aff ects 1% to Th e phenotypic appearance of psoriasis is due to 3% of the population worldwide. Although hyperproliferation and abnormal diff erentiation of Ppsoriasispsoriasis iiss uundoubtedlyndoubtedly ddistressing,istressing, aaffff eectedcted iindi-ndi- keratinocytes, infl ammatory cell infi ltration, and viduals are typically otherwise healthy and thus well vascular changes (Figure 1). Th ese changes appear suited to thoughtful outpatient care. to be initiated by immunologic mechanisms, namely, Recent advances in our understanding of pso- the T lymphocyte. A great deal of research, how- riasis have provided parallel advances in topical ever, is still uncovering the details of the immune treatments. Appropriate knowledge and use of system’s involvement in pathogenesis of psoriasis. these therapies is vital to both dermatologists and family physicians caring for patients with psoriasis. Topical therapies Despite our evolving comprehension of the patho- genesis of psoriasis, no lasting cure has been found; Quality of evidence lifetime control is often necessary. Therapeutic MEDLINE was searched from 1987 to 2003 using options abound; frequent advances have been the search term “psoriasis” combined with “topi- made in topical therapies, systemic treatments, and cal treatment.” Articles were selected based on phototherapies. Since an estimated 75% of psori- relevance, quality, and originality; 127 abstracts atic patients have mild-to-moderate disease,1 topi- were reviewed. Additional articles were identified cal treatments remain the most widely used. Th ese from the reference lists of the papers selected. are efficacious in mild-to-moderate Thirty-eight articles were included in the final disease and provoke less concern about systemic review. side eff ects. Levels of evidence of the cited articles are cat- Th is review highlights the effi cacies and adverse egorized according to the Canadian Task Force effects of topical treatments, as well as the evi- on Preventative Health Care. Of the studies, 58% dence and rationale for combining therapies. It is were level I (randomized controlled trial, sys- important to note that several excellent reviews tematic review, or meta-analysis) and 21% were of topical psoriasis therapies have been written.2-4 level II (non-randomized, cohort, case-control, Th e purpose of this review is to discuss additional or epidemiologic studies). The remaining articles developments, to include data comparing various included four basic science papers (10.5%) and treatments, and to update family physicians who four review articles (10.5%). No level III arti- treat a great number of patients with psoriasis. cles were included (expert opinion or consensus statements). Corticosteroids. Corticosteroids form the basis of topical psoriasis treatment in North America. Th ey Dr Afi fi is a fi rst-year dermatology resident at the are effi cacious, are well tolerated, and come in a University of Manitoba in Winnipeg. Dr de Gannes is variety of forms. Several potencies are available, a fourth-year resident in dermatology at the University ranging from Class 1 (highest potency) to Class 7 of British Columbia in Vancouver. Dr Huang is an (Table 15). Th e ability to vary strength and admin- Associate Professor in Dermatology in the Department istration method gives steroids the versatility to of Dermatology at Tongji Medical College of the Central tread lightly on sensitive or thinly skinned areas, China University of Science and Technology in Wuhan, such as the face and body folds, and the power Hubei Province, China. Dr Zhou is an Assistant to treat more resistant areas of the body, such as Professor in Dermatology in the Department of Medicine, extensor surfaces and the soles of the feet. Division of Dermatology, at the University of British Recently, Mason et al1 analyzed data from all ran- Columbia. domized placebo-controlled trials involving topical

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Figure 1. Appearance of psoriasis: A) Nail pitting; B) Lesions on the back; C) Infl ammatory areas on the buttocks; D) Lesion on the back of the calf.

A

B

C D

psoriasis treatments and all randomized head-to- Levels of evidence head studies involving vitamin D3 derivatives pub- lished between 1966 and 1999. The statistically pooled data spanned 3380 patients randomized Level I: At least one properly conducted ran- in 41 placebo-controlled trials and 4898 patients domized controlled trial, systematic review, or in head-to-head trials. Even though all treatments meta-analysis (including steroids, vitamin D3 derivatives, anthra- Level II: Other comparison trials, non-randomized, lin, and ) outperformed placebo, the very potent cohort, case-control, or epidemiologic studies, and steroids were found to be the most effi cacious (level preferably more than one study I evidence). More recently, foam preparations of Level III: valerate and propionate, Expert opinion or consensus statements which were originally developed for scalp psoriasis,

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have been shown to be eff ective in treating nonscalp to comply with treatment. Unfortunately, the foams psoriasis as well (level I evidence).6,7 Th at these prep- are not yet available in Canada. arations are eff ective is important, because patients With such clear benefi ts, the only limit to corti- fi nd them more acceptable and are thus more likely costeroids is their side eff ects. Th ese include local Table 1. Potency of topical corticosteroids available in Canada cutaneous reactions, such as atrophy, telangiec- NAME OINTMENT CREAM LOTION tases, striae, traumatic purpura, perioral dermati- CLASS I: SUPERPOTENT* tis, hypertrichosis, and rarely, contact dermatitis. Betamethasone dipropionate x x x Th ese eff ects are more likely to occur in sensitive glycol 0.05% areas, such as the face and intertriginous areas. 8 Clobetasol 17-propionate 0.05% x x x Adrenal suppression has also been reported, but Halobetasol propionate 0.05% x x appears to be serious only with very widespread 9 CLASS II/III: HIGH POTENCY* use or in infants. 0.1% x x In a systematic review of randomized or Betamethasone dipropionate x x double-blind trials evaluating the adverse eff ects 10 (ointment, cream) 0.05% of topical psoriasis treatments, Bruner et al found 0.25% x x that corticosteroids had the lowest rate of adverse Difl ucortolone valerate 0.1% x x events (ranging from 3.2% to 23%, level I evi- 0.05% x x dence). propionate was at the low end 0.1% x x x of this range. Dose regimens, such as pulse deliv- furoate (ointment) x ery (application of topical weekly instead of 0.1% daily as described below), both minimize cumula- acetonide 0.5% x tive exposure and reduce local side eff ects (level 11 12 CLASS IV/V: MODERATE POTENCY* I evidence). For instance, Lebwohl et al found Betamethasone dipropionate x that using twice daily for (lotion) 0.05% 2 weeks and then once daily for 2 days of the week 0.1% x x x for 8 weeks was eff ective and did not cause atrophy 17-butyrate 0.05% x x in steroid-sensitive areas. One fi nal problem with (ointment) 0.05% x steroid treatment is development of tachyphylaxis Desoximetasone 0.05% x (tolerance to the action of a drug after repeated 13 Fluocinonide 0.025% x x doses) with prolonged use. Some studies have failed to fi nd this eff ect.14 Nevertheless, pulsed dos- 17-valerate 0.2% x x ing can eliminate this concern. Mometasone furoate x x (cream, lotion) 0.1% 0.1% x x . Topical vitamin D analogues 0.1% x x x are thought to inhibit keratinocyte growth, promote CLASS VI/VII: LOW POTENCY* keratinocyte diff erentiation, and decrease infl amma- tion in psoriatic lesions via vitamin D receptors on Betamethasone valerate 0.05% x x x keratinocytes and T lymphocytes.15,16 is Desonide (cream, lotion) 0.05% x x available in North America, while calcipotriol, cal- Fluocinonide 0.01% x x citriol, and are off ered in Europe. Hydrocortisone 1.0%, 2.5% x x x Th is class has fared well in effi cacy studies, per- 0.5%, x x forming as well as midpotency steroids,17,18 but less 1.0% well than superpotent steroids (level I evidence). Prednicarbate 0.05% x x These results are supported by the Mason and Triamcinolone acetonide 0.025% x associates1 study, which found that vitamin D ana- *Potency class based on the Stoughton vasoconstrictor assay.5 logues were as eff ective as all but the very potent

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steroids in placebo-controlled trials (level I evi- induces a dose-dependent local dence). A recent randomized trial of 258 psoriasis irritation, with itching, burning, and erythema.23 patients treated with either or betameth- Tazarotene was found to have a slightly higher inci- asone dipropionate 0.05% ointment found that, dence of adverse effects than corticosteroids or while betamethasone performed slightly better on vitamin D analogues (range 13% to 50%), but less two of three efficacy measures, the calcitriol group than anthralin or tar (level I evidence).10 remained in remission longer (level I evidence).19 Whether or not calcipotriol also induces a longer Anthralin. Although anthralin () is a time- remission period requires clarification. honoured treatment for psoriasis, its staining and Overall, vitamin D analogues are tolerated irritating effects limit its use to recalcitrant dis- well; the most common adverse effect is a mild ease. The precise efficacy of anthralin is difficult to irritant contact dermatitis. The face and body ascertain, as few studies have adequate enrolment. folds are more prone to this effect, with irrita- Moreover, anthralin is more commonly used in tion developing in up to 20% of patients treated conjunction with ultraviolet B phototherapy in in those areas.20 Hypercalcemia has also been current practice. The study by Mason and associ- reported, but this appears inconsequential in ates,1 however, did include data from five head-to- treatment doses.21 In the study by Bruner and col- head trials with vitamin D derivatives. Analysis leagues10 of adverse events with topical therapies, revealed anthralin to be less effective than other vitamin D analogues were found to have the sec- derivatives (level I evidence). ond lowest rate of adverse events (range of 4.8% Anthralin’s adverse effects include local irritation to 35%, level I evidence). Tacalcitol was the least and staining of skin, clothing, and furniture. Recent irritating. attempts to reduce these effects include a short-con- tact regimen (topical therapy applied to skin daily Retinoids. Oral retinoids have been used in the for a short period [5 to 30 minutes] then washed treatment of psoriasis for some time. A topical reti- off),26 heat-sensitive preparations,27 and use of tri- noid, tazarotene, is a more recent innovation. It is ethanolamine to prevent staining.28 These variations believed to act at the gene level, via retinoic acid have not reduced the effectiveness of the treatment. receptors, which mediate keratinocyte proliferation and differentiation.22 Tar. Like anthralin, tar has been used on psoriasis Studies of the efficacy of tazarotene lag behind for a long time. The main form used, , is a those of vitamin D analogues and corticosteroids. by-product of coal distillation and contains more One placebo-controlled trial of tazarotene,23 than 10 000 compounds. Its effect is likely medi- involving 318 patients, was included in the study by ated by DNA suppression.29 Recent randomized Bruner and colleagues.10 Tazarotene’s performance controlled trials comparing coal tar and calcipot- was equivalent to the potent steroid and vitamin D riol have shown comparable clinical efficacy (cal- groups (level I evidence). Success rates, defined as cipotriol has a faster onset of action) and similar 50% improvement or more, were 52% and 70% for relapse rates (level I evidence). 30,31 Calcipotriol is the 0.05% and 0.1% gels, respectively. The effects better tolerated and has a better cosmetic appear- were maintained for 12 weeks after treatment. ance. Coal-tar preparations continue to be consid- Similar results have been seen in trials published erably less expensive than calcipotriol. since that time.24 Although there were no head-to- Tar is infrequently used for outpatients with pso- head studies with vitamin D analogues to include riasis, as it can cause acne, folliculitis, phototoxic- in the study by Mason and associates,1 a compari- ity, and local irritation, and it can be messy and can son of 0.05% fluocinonide with tazarotene found stain. Although occupational exposure has been the to have comparable efficacy and a lon- linked to , use of tar treatment has not ger remission period (level I evidence).25 (level II evidence).32

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Combination therapies EDITOR’S KEY POINTS Corticosteroids and vitamin D analogues. In • Psoriasis is a psychologically and sometimes medically disabling general, the combination of corticosteroids and condition aff ecting 1% to 3% of the population. Most patients are vitamin D derivatives is more efficacious than managed by family physicians. either therapy alone and produces fewer side • The goal of treatment is lifetime control. About 75% of patients have effects. Randomized trials have demonstrated mild-to-moderate psoriasis, amenable to topical treatment. • Corticosteroids form the basis of treatment, with the best success this for several steroid-calcipotriol pairings (level and fewest side eff ects. Since they come in various potencies, they 33-35 I evidence). The calcipotriol and betameth- permit individualized treatment depending on severity of the condi- asone dipropionate combination is now avail- tion and site on the body. Pulsed delivery (once weekly) can mini- able premixed, providing increased convenience. mize side eff ects. Since corticosteroids are anti-inflammatory, • Other treatments include vitamin D analogues (calcipotriol), reti- they tend to reduce the irritation of calcipotriol. noids (tazarotene), anthralin (dithranol), tar compounds, or combi- nations (such as steroids and vitamin D). Conversely, calcipotriol can serve as a steroid- 3 sparing agent, reducing its side effects. Thus, POINTS DE REPÈRE DU RÉDACTEUR an improved side effect profile is not surprising. • Le psoriasis, qui touche de 1% à 3% de la population, est une source This theoretical advantage is not always borne de problèmes psychologiques et parfois médicaux. La plupart des out, though; some studies find a slight increase in cas sont traités par les médecins de famille. side effects when therapies are combined (level I • Le but du traitement est un contrôle à vie. Environ 75% des patients evidence).10 ont une forme bénigne ou modérée de psoriasis qui répond au trai- tement topique. • Les corticostéroïdes sont la pierre angulaire du traitement, avec le Corticosteroids and tazarotene. Akin to the pre- meilleur taux de succès et le moins d’eff ets indésirables. Leur poso- vious combination, steroids and tazarotene seem logie variée permet d’adapter le traitement à la gravité de l’aff ection a good complement. Indeed, studies have found et au site anatomique touché. On peut minimiser les eff ets indésira- this combination to be more eff ective than mono- bles par une administration hebdomadaire unique. therapy (level I evidence).36 Adding tazarotene • Parmi les autres traitements, mentionnons les analogues de la vitamine D (calcipotriol), les rétinoïdes (tazarotène), l’anthraline to a steroid can also circumvent the problem of (dithranol), les composés à base de goudron ou les combinaisons tachyphylaxis, as duration of treatment benefit (par ex., stéroïdes et vitamine D). and length of remission are prolonged (level I evi- dence).37 An interesting result of this combination is that each has the opposite eff ect on epidermal Conclusion thickness. Whereas steroids induce atrophy, taz- Psoriasis is a disease without a lasting cure. Yet it arotene increases epidermal thickness. Hence, the is the subject of active research that provides fre- combination has been shown to reduce the degree quent therapeutic advances. As knowledge pro- of steroid-induced atrophy by as much as 37% gresses, more efficacious treatments with fewer (level II evidence).38 Last, tazarotene-induced irri- side eff ects become available. Awareness of these tation is reduced by the anti-infl ammatory eff ect advances in therapy is the responsibility of physi- of a steroid. cians caring for patients with psoriasis. Corticosteroids remain central to treatment, but Corticosteroids and salicylic acid. Salicylic vitamin D analogues are important to use either in acid is a useful adjunct in treating psoriasis that conjunction with or as an alternative to steroids. reduces scale and softens lesions. It too has proven Owing to their ability to induce long remission valuable in combination: it enhances steroid effi - periods, use of retinoids is also likely to increase cacy by increasing penetration (level I evidence).39 over time. Th e combination of steroids and these Since this might be of concern with respect to sys- two newer medications is perhaps the most prom- temic toxicity, some authors suggest combining ising current treatment, as increased effi cacy and salicylic acid with a mid-potency steroid.3 fewer side eff ects seem to result. Because in general

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there is wide variation in patients’ psoriatic presen- 5. Stoughton RB. Vasoconstrictor activity and percutaneous absorption of glucocorticoste- roids. Arch Dermatol 1969;99:753-6. tations, both in terms of location and in disease 6. Lebwohl M, Sherer D, Washenik K, Krueger GG, Menter A, Koo J, et al. A randomized, double-blind, placebo-controlled study of 0.05% foam in the treat- severity, individualized approaches are indicated ment of nonscalp psoriasis. Int J Dermatol 2002;41:269-74. 7. Stein LF, Sherr A, Solodkina G, Gottlieb AB, Chaudhari U. Betamethasone valerate foam in choosing specific treatments. The scheme in for treatment of nonscalp psoriasis. J Cutan Med Surg 2001;5(4):303-7. 8. Katz HI, Hien NT, Prawer SE. Superpotent treatment of psoriasis vulgaris— clinical effi cacy and adrenal function. J Am Acad Dermatol 1987;16:804-11. Table 2 provides a framework that can be altered 9. Turpeinen M, Salo OP, Leisti S. Eff ect of percutaneous absorption of hydrocortisone on adrenocortical responsiveness in infants with severe skin disease. Br J Dermatol to suit the needs of individual patients. 1986;115:475-84. 10. Bruner CR, Feldman SR, Ventrapragada M, Fleischer AB Jr. A systematic review of Table 2. Approach to treatment adverse eff ects associated with topical treatments for psoriasis. Dermatol Online J 2003;9(1):2. Mild-to-moderate plaque psoriasis 11. Katz HI, Prawer SE, Medansky RS, Krueger GG, Mooney JJ, Jones ML, et al. Intermittent maintenance treatment of psoriasis: a double-blind multi-center trial of • Betamethasone dipropionate–calcipotriol combination augmented betamethasone dipropionate ointment in a pulse dose treatment regimen. Dermatologica 1991;183:269-314. • Corticosteroid (moderate to high potency) 12. Lebwohl MG, Tan MH, Meador SL, Singer G. Limited application of fl uticasone propio- nate ointment 0.005% in patients with psoriasis of the face and intertriginous areas. J Am Acad Dermatol 2001;44:77-82. • Calcipotriol 13. Du Vivier A, Stoughton RB. Tachyphylaxis to the action of topically applied corticoste- roids. Arch Dermatol 1975;111:581-3. • Tazarotene-corticosteroid combination 14. Miller JJ, Roling D, Margolis D, Guzzo C. Failure to demonstrate therapeutic tachy- phylaxis to topically applied steroids in patients with psoriasis. J Am Acad Dermatol • Tazarotene 1999;41:546-9. 15. Gerritsen MJ, Rulo HF, Van Vlijmen-Willems I, Van Erp PE, van de Kerkhof PC. Topical

• Others: tar, anthralin treatment of psoriatic plaques with 1,25-dihydroxyvitamin D3: a cell biologic study. Br J Dermatol 1993;128:666-73. Facial or intertriginous psoriasis: Low-potency corticosteroid 16. Reichtrath J, Perez A, Muller SM, Chen TC, Kerber A, Bahmer FA, et al. Topical calcitriol (1,25-dihydroxyvitamin D3) treatment of psoriasis: an immunohistological evaluation. Acta (ie, hydrocortisone 1% cream or ointment) Derm Venereol (Stockh) 1997;77:268-72. 17. Kragballe K, Gjertsen BT, De Hoop D, Karlsmark T, van de Kerkhof PC, Larko O, et al. Scalp psoriasis Double-blind, right/left comparison of calcipotriol and betamethasone valerate in treat- ment of psoriasis vulgaris. Lancet 1991;337:193-6. • Corticosteroid lotion (ie, betamethasone valerate, clobetasol) 18. Cunliff e WJ, Berth-Jones J, Claudy A, Fairiss G, Goldin D, Gratton D, et al. Comparative study of calcipotriol (MC 903) ointment and betamethasone 17-valerate ointment in • Corticosteroid scalp oil or (fl uocinonide) patients with psoriasis vulgaris. J Am Acad Dermatol 1992;26:736-43. 19. Camarasa JM, Ortonne JP, Dubertret L. Calcitriol shows greater persistence of treatment eff ect than betamethasone dipropionate in topical psoriasis therapy. J Dermatol Treat • Corticosteroid foam (where available) 2003;14(1):8-13. 20. Lebwohl M, Ali S. Treatment of psoriasis. Part 1. Topical therapy and phototherapy. J Am • Calcipotriol lotion Acad Dermatol 2001;45:487-502. 21. Mortensen L, Kragballe K, Wegmann E, Schifter S, Risteli J, Charles P. Treatment of pso- • Tar shampoo riasis vulgaris with topical calcipotriol has no short-term eff ect on calcium or bone metab- olism: a randomized, double-blind, placebo-controlled study. Acta Derm Venereol (Stockh) Palmar or plantar psoriasis 1993;73:300-4. 22. Duvic M, Nagpal S, Asano AT, Chandraratna RA. Molecular mechanisms of tazarotene • High to superpotent corticosteroid action in psoriasis. J Am Acad Dermatol 1997;37(2 Pt 3):S18-S24. 23. Weinstein GD, Krueger GG, Lowe NJ, Duvic M, Friedman DJ, Jegasothy BV, et al. • Betamethasone dipropionate–salicylic acid combination Tazarotene gel, a new retinoid, for topical therapy of psoriasis: vehicle-controlled study of safety, effi cacy, and duration of therapeutic eff ect. J Am Acad Dermatol 1997;37:85-92. 24. Weinstein GD, Koo JY, Krueger GG. Tazarotene cream in the treatment of psoriasis: two • Consider referral to a dermatologist for phototherapy multicenter, double-blind, randomized, vehicle-controlled studies of the safety and effi cacy (topical -UV-A) if refractory of tazarotene creams 0.05% and 0.1% applied once daily for 12 weeks. J Am Acad Dermatol 2003;48:760-7. Severe widespread psoriasis or psoriasis refractory to topical therapy: 25. Lebwohl M, Ast E, Callen JP. Once-daily tazarotene gel versus twice-daily fl uocinonide cream in the treatment of plaque psoriasis. J Am Acad Dermatol 1998;38:705-11. Refer to a dermatologist for phototherapy or systemic therapy 26. Runne U, Kunze J. Short duration (“minutes”) therapy with dithranol for psoriasis: a new outpatient regimen. Br J Dermatol 1982;106:135-9. Psoriatic arthritis: Consider referral to a rheumatologist for arthritis 27. Volden G, Bjornberg A, Tegner E, Pedersen NB, Arles UB, Agren S, et al. Short-contact treatment at home with Micanol. Acta Derm Venereol Suppl (Stockh) 1992;172:20-2. management 28. Ramsay B, Lawrence CM, Bruce JM, Shuster S. Th e eff ects of triethanolamine applica- tion on anthralin-induced infl ammation and therapeutic eff ect in psoriasis. J Am Acad Dermatol 1990;23:73-6. Competing interests 29. Walter JF, Stoughton RB, DeQuoy PR. Suppression of epidermal proliferation by ultravio- let light, coal tar and anthralin. Br J Dermatol 1978;99:89-96. None declared 30. Sharma V, Kaur I, Kumar B. Calcipotriol versus coal tar: a prospective randomized study in stable plaque psoriasis. Int J Dermatol 2003;42:834-8. 31. Tzaneva S, Honigsmann H, Tanew A. Observer-blind, randomized, intrapatient compari- son of a novel 1% coal tar preparation (Exorex) and calcipotriol cream in the treatment of Correspondence to: Dr Y. Zhou, Division of plaque type psoriasis. Br J Dermatol 2003;149:350-3. 32. Jemec GBE, Osterlind A. Cancer in patients treated with coal tar: a long-term follow up Dermatology, 835 W 10th Ave, Vancouver, BC V5Z 4E8; study. J Eur Acad Dermatol Venereol 1994;3(2):153-6. 33. Kragballe K, Barnes L, Hamber KJ. Calcipotriol cream with or without concurrent topical telephone (604) 875-4747; fax (604) 873-9919; e-mail corticosteroid in psoriasis: tolerability and effi cacy. Br J Dermatol 1998;139:649-54. 34. Austad J, Bjerke JR, Gjertsen BT. Clobetasol propionate followed by calcipotriol is supe- [email protected] rior to calcipotriol alone in topical treatment of psoriasis. J Eur Acad Dermatol Venereol 1998;11(1):19-24. 35. Papp KA, Guenther L, Boyden B. Early onset of action and effi cacy of a combination of calcipotriene and betamethasone dipropionate in the treatment of psoriasis. J Am Acad Dermatol 2003;48:48-54. References 36. Lebwohl MG, Breneman DL, Goff e BS. Tazarotene 0.1% gel plus corticosteroid cream in 1. Mason J, Mason AR, Cork MJ. Topical preparations for the treatment of psoriasis: a sys- the treatment of plaque psoriasis. J Am Acad Dermatol 1998;39:590-6. tematic review. Br J Dermatol 2002;146:351-64. 37. Lebwohl M, Lombardi K, Tan MH. Duration of improvement of psoriasis after treatment 2. Greaves MW, Weinstein GD. Treatment of psoriasis. Drug Th er 1995;332(9):581-7. with tazarotene 0.1% gel plus clobetasol propionate 0.05% ointment: comparison of main- 3. Endzweig-Gribetz CH, Brady C, Lynde C, Sibbald D, Lebwohl M. Drug interactions in tenance treatments. Int J Dermatol 2001;40:64-6. psoriasis: the pros and cons of combining topical psoriasis therapies. J Cutan Med Surg 38. Kaidbey K, Kopper SC, Sefton J, Gibson JR. A pilot study to determine the eff ect of tazar- 2002;6(3 Suppl):12-6. otene 0.1% gel on steroid-induced epidermal atrophy. Int J Dermatol 2001;40:468-71. 39. Koo J, Cuffi e CA, Tanner DJ, Bressinck R. Mometasone furoate 0.1%–salicylic acid 5% 4. Tremblay JF, Bissonnette R. Topical agents for the treatment of psoriasis, past, present and ointment versus mometasone furoate 0.1% ointment in the treatment of moderate-to- future. J Cutan Med Surg 2002;6(3 Suppl):8-11. severe psoriasis: a multicenter study. Clin Th er 1998;20(2):283-91.

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