K. M. Cordoro, MD
Department of Dermatology, University of California, San Francisco, CA, USA
Psoriasis represents a potentially life-altering disease that can profoundly impact physical, emotional and social functioning, and overall quality of life. The majority of cases are mild and managed adequately with topical medications. A minor subset of children present with severe, rapidly evolving disease that requires systemic therapy. The choice of treatment in children, as in adults, is determined by disease acuity, morphology, distribution, severity and the presence of comorbidities such as psoriatic arthropathy. Practical considerations such as ease of use, patient acceptability, accessibility, risk to benefit ratio, cost and individual perceptions of disease and quality of life are factored into treatment decisions. Part I of this 2-part series will focus on topical agents, their varying degrees of effectiveness, potential side-effects and applications in clinical practice.
anthralin, calcineurin inhibitors, calcipotriene/ calcipotriol, children, coal tar, corticosteroids, psoriasis, salicylic acid
Monotherapy may be effective for limited, focal or mild disease. In cases where multiple medications are necessary, the number of agents that must be applied can be reduced by compounding compatible agents. Research the surrounding community and keep a list of compounding pharmacies to provide to your patients. Ointment formulations tend to have greater efficacy than creams but some patients, particularly adolescents, find them objectionable. In an effort to increase compliance, prescribe whichever vehicle the patient finds preferable.1 Thick, greasy ointments can be used at nighttime and more cosmetically acceptable creams, lotions and solutions reserved for daytime use.
Corticosteroids remain among the first line agents in the topical treatment of psoriasis in all age groups. Delivering the steroid to the involved skin in a convenient, tolerable, safe and efficacious manner requires selection of a vehicle that is well-suited to site-specific qualities such as hair (scalp), moisture (intertriginous zones) and occlusion (axillae, diaper area, gluteal cleft). A variety of vehicles are available to choose from and include powders, sprays, lotions, solutions, creams, emollient creams, ointments, gels, tape and foam.2 Thin and intertriginous skin responds to lower potencies and thick hyperkeratotic areas such as the palms and soles require high potency agents. Infants have a large body surface area that increases the chance of systemic absorption and adverse events, such as adrenal suppression.3 In general, very high potency agents should be avoided in children, if possible, or used sparingly in combination or rotation with steroid sparing alternatives such as coal tar, anthralin, calcipotriene and topical calcineurin inhibitors.
Crude coal tar has antipsoriatic, antiseborrheic, antipruritic and keratolytic effects.4 Given its better cosmetic acceptability, liquor carbonis detergens (LCD), a modified, less clinically active coal tar, has largely replaced crude coal tar in the outpatient setting. It can be compounded in an ointment, cream or solution vehicle in concentrations from 0.5% to 20%. Tar is a safe, effective treatment for childhood psoriasis and is supplied in a variety of topical formulations and shampoos. It can be used alone or compounded with corticosteroids, lactic and salicylic acid. Its safety, efficacy, and relatively low cost, compared with other topical agents are advantages in the long-term treatment of psoriasis. Side-effects of tar include folliculitis, irritation, and photosensitivity. It should not be used on acutely inflamed skin, or on pustular or erythrodermic psoriasis.5 There is no definitive evidence of an increased risk of skin cancer above the expected incidence for the general population from the use of therapeutic tar.6,7 Education regarding the favorable safety profile and place in therapy as a steroid-sparing adjunct may increase tolerance and compliance of this excellent and underutilized topical therapy.
Anthralin (dithranol) is a potent anti-inflammatory and anti-proliferative agent.8 It is a synthetic version of chrysarobin, a natural substance derived from the araroba tree of South America used to treat psoriasis for nearly 100 years.9 Negligible systemic absorption is responsible for its excellent safety profile and ease of use, especially in children. Its use has been limited due to staining and irritation, but short contact and “minutes” therapy are popular, less messy alternatives (increasing concentrations [0.1% to 3%] of dithranol applied to the skin and left in place for 10-30 minutes daily until a slight irritation develops, then hold dose/time until clear10). Lower concentrations or less contact time should be maintained on more sensitive sites such as anogenital skin.
Calcipotriene (calcipotriol in Europe and Canada) is an analog of vitamin D3 that has been proven safe and effective in adults with psoriasis. It is an efficient nonsteroidal alternative and has utility as monotherapy as well as in novel sequential and rotational combinations with topical steroids.11 Calcipotriol ointment has been shown to be effective, well tolerated and safe in children with psoriasis, with local irritation the most commonly reported side-effect.12-15 Adverse effects of topical calcipotriol on systemic calcium homeostasis in adult patients with chronic plaque psoriasis has been evaluated and is related to dose per unit body weight of the patient.16 Though no formal guidelines exist for children, use of up to 45g/week per m2 in children does not seem to influence serum ionized calcium levels.13 Regimens combining calcipotriene and topical steroids, such as once daily use of each or twice daily use of calcipotriene on weekdays and steroids on weekends only, are steroid sparing and superior in efficacy to twice daily monotherapy with either agent.17,18 Calcipotriene destabilizes in the presence of salicylic acid, ammonium lactate, and hydrocortisone valerate 0.2% ointment and thus, should not be used at the same time as or compounded with these molecules.19
Tazarotene is a third-generation topical retinoid US FDA-approved for once daily treatment of psoriasis in adults aged 18 and older and acne vulgaris in patients aged 12 and above. Similar to other retinoids, tazarotene restores normal epidermal differentiation and proliferation and reduces epidermal inflammation.20 Limit its use to thicker plaques on non-intertriginous sites. Tazarotene is neither sensitizing nor phototoxic, but dose-related skin irritation is common and often necessitates combination with a topical steroid applied at a different time of day. Short contact (10-60 minutes per day, then wash off), alternate day or weekly applications are potential ways to include this useful agent in sequential and rotational regimens. Effectiveness of tazarotene for nail psoriasis has been demonstrated clinically in adults21 and children.22
Topical Calcineurin Inhibitors
Tacrolimus and pimecrolimus are nonsteroidal immunomodulating macrolactams that work by blocking the enzyme calcineurin, ultimately inhibiting the downstream production of IL-2 and subsequent T-cell activation and proliferation.23 Both topical agents are currently FDA approved for second line intermittent treatment of atopic dermatitis in patients aged 2 years and older (pimecrolimus and tacrolimus 0.03%) and aged 15 and older (tacrolimus 0.1%). They are effective, safe and well tolerated therapeutic options for psoriasis at sites more sensitive to the long-term adverse effects of topical steroids such as the face, flexures, and anogenital region.24-27
Salicylic acid is a useful adjunctive keratolytic agent for very thick localized plaques arising on the scalp, palms and soles. It should be used sparingly and with caution in the pediatric population because of the risk of percutaneous salicylate intoxication.28 Avoid its use altogether in infants and children less than 6 years old.
Treatment of childhood psoriasis is both challenging and rewarding. Medical management remains primarily anecdotal as most therapies are neither studied nor approved for use in children. At our disposal are both traditional and new topical agents that can be used in diverse ways as monotherapy or in combination. Treatment decisions must be individualized for each patient based on thorough assessment of the disease, comorbidities, and impact on quality of life.
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- Maibach HI, Wester RC. Issues in measuring percutaneous 3. absorption of topical corticosteroids. Int J Dermatol 31(Suppl 1):21-5 (1992 Oct).
- Cram DL. Psoriasis: treatment with a tar gel. 4. Cutis 17(6):1197-8, 1202-3 (1976 Jun).
- Comaish JS. Tar and related compounds in the therapy of 5. psoriasis. Clin Exp Dermatol 6(6):639-45 (1981 Nov).
- Pion IA, Koenig KL, Lim HW. Is dermatologic usage of coal 6. tar carcinogenic? A review of the literature. Dermatol Surg 21(3):227-31 (1995 Mar).
- Pittelkow MR, Perry HO, Muller SA, et al. Skin cancer in 7. patients with psoriasis treated with coal tar. A 25-year follow-up study. Arch Dermatol 117(8):465-8 (1981 Aug).
- Reichert U, Jacques Y, Grangeret M, et al. Antirespiratory 8. and antiproliferative activity of anthralin in cultured human keratinocytes. J Invest Dermatol 84(2):130-4 (1985 Feb).
- Ashton RE, Andre P, Lowe NJ, et al. Anthralin: historical and 9. current perspectives. J Am Acad Dermatol 9(2):173-92 (1983 Aug).
- Runne U, Kunze J. Short-duration (‘minutes’) therapy with 10. dithranol for psoriasis: a new out-patient regimen. Br J Dermatol 106(2):135-9 (1982 Feb).
- Koo JY. New developments in topical sequential therapy for 11. psoriasis. Skin Therapy Lett. Nov 2005;10(9):1-4 (2005 Nov).
- Choi YJ, Hann SK, Chang SN, et al. Infantile psoriasis: successful 12. treatment with topical calcipotriol. Pediatr Dermatol 17(3):242-4 (2000 May-Jun).
- Darley CR, Cunliffe WJ, Green CM, et al. Safety and efficacy 13. of calcipotriol ointment (Dovonex) in treating children with psoriasis vulgaris. Br J Dermatol 135(3):390-3 (1996 Sep).
- Oranje AP, Marcoux D, Svensson A, et al. Topical calcipotriol 14. in childhood psoriasis. J Am Acad Dermatol 36(2 Pt 1):203-8 (1997 Feb).
- Travis LB, Silverberg NB. Psoriasis in infancy: therapy with 15. calcipotriene ointment. Cutis 68(5):341-4 (2001 Nov).
- Bourke JF, Mumford R, Whittaker P, et al. The effects of topical 16. calcipotriol on systemic calcium homeostasis in patients with chronic plaque psoriasis. J Am Acad Dermatol 37(6):929-34 (1997 Dec).
- Koo J, Blum RR, Lebwohl M. A randomized, multicenter study 17. of calcipotriene ointment and clobetasol propionate foam in the sequential treatment of localized plaque-type psoriasis: short- and long-term outcomes. J Am Acad Dermatol 55(4):637-41 (2006 Oct).
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- Esgleyes-Ribot T, Chandraratna RA, Lew-Kaya DA, et al. 20. Response of psoriasis to a new topical retinoid, AGN 190168. J Am Acad Dermatol 30(4):581-90 (1994 Apr).
- Bianchi L, Soda R, Diluvio L, et al. Tazarotene 0.1% gel for 21. psoriasis of the fingernails and toenails: an open, prospective study. Br J Dermatol 149(1):207-9 (2003 Jul).
- Diluvio L, Campione E, Paterno EJ, et al. Childhood nail 22. psoriasis: a useful treatment with tazarotene 0.05%. Pediatr Dermatol 24(3):332-3 (2007 May-Jun).
- Nghiem P, Pearson G, Langley RG. Tacrolimus and pimecrolimus: 23. from clever prokaryotes to inhibiting calcineurin and treating atopic dermatitis. J Am Acad Dermatol 46(2):228-41 (2002 Feb).
- Amichai B. Psoriasis of the glans penis in a child successfully 24. treated with Elidel (pimecrolimus) cream. J Eur Acad Dermatol Venereol 18(6):742-3 (2004 Nov).
- Brune A, Miller DW, Lin P, et al. Tacrolimus ointment is effective 25. for psoriasis on the face and intertriginous areas in pediatric patients. Pediatr Dermatol 24(1):76-80 (2007 Jan-Feb).
- Mansouri P, Farshi S. Pimecrolimus 1% cream in the treatment of 26. psoriasis in a child. Dermatol Online J 12(2):7 (2006).
- Steele JA, Choi C, Kwong PC. Topical tacrolimus in the 27. treatment of inverse psoriasis in children. J Am Acad Dermatol 53(4):713-6 (2005 Oct).
- Taylor JR, Halprin KM. Percutaneous absorption of salicylic 28. acid. Arch Dermatol 111(6):740-3 (1975 Jun).