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Management of Pediatric Psoriasis

Tina Bhutani, MD; Faranak Kamangar, BSc; and Kelly M. Cordoro, MD

soriasis is a chronic inflammatory disease of the skin, nails, and joints. Overall prevalence in the US is 2.5%.1-3 Among children aged 0 to 18 years, prevalence is 1% and incidence is 40.8 per 100,000.4

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EDUCATIONAL OBJECTIVES

1. Provide a practical approach to the management of psoriasis in the pediatric primary care setting. 2. Review the proper selection and utilization of topical agents for the management of pediatric psoriasis. 3. Recognize moderate-to-severe psoriasis and when referral to a dermatologist for advanced management is indicated.
Tina Bhutani, MD, is Clinical Research Fellow, UCSF Psoriasis and Skin Treatment Center, UCSF Department of Dermatology. Faranak Kamangar, BSc, is Clinical Research Associate, UCSF Psoriasis and Skin Treatment Center UCSF Department of Dermatology. Kelly M. Cordoro, MD, is Assistant Professor of Clinical Dermatology and Pediatrics, University of California, San Francisco. Address correspondence to: Kelly M. Cordoro, MD, University of California, San Francisco; fax: 415-353-7478; email: cordorok@ derm.ucsf.edu. Dr. Bhutani and Ms. Kamangar have disclosed no relevant financial relationships. Dr. Cordoro has disclosed the following relevant financial relationships: consulting fees, Topaz Pharmaceuticals. doi: 10.3928/00904481-20111209-08

More than one-third of patients present before age 20.5-9 The pattern of psoriasis presentation in children can vary from what is classically observed in adults. Children have increased involvement of the face and anogenital regions, and pruritus is common.10 Plaque-type psoriasis is most common (73.7%)4 and presents as erythematous plaques with silvery-white scales typically involving the scalp, postauricular region (Figure 1a, see page e2), elbows, knees, umbilicus, and buttocks (Figure 1b, see page e2). Guttate psoriasis is the next most common type (13.7%);4 it is composed of few to numerous small (less than 1 cm), drop-like erythematous scaly papules (Figure 1c, see page e2). Guttate psoriasis has a documented association with pharyngeal and less commonly perianal, streptococcal infection.11 Other common types are inverse psoriasis, involving the skin folds and flexures (neck, axillae, groin), and psoriasis in the anogenital area (diaper or napkin psoriasis). Diaper psoriasis is especially common in children younger than 2 years of age and presents as bright- to dull-red smooth or slightly scaly erythema in the diaper area, which may be accompanied by more typical psoriasis in other locations (Figure 1d, see page e2). Pustular and erythrodermic psoriasis are uncommon subtypes in young

children10 but, when present, are typically accompanied by systemic signs, including fever, chills, malaise, and subsequent dehydration and toxicity. Nail involvement such as pitting, onycholysis, and subungual debri can occur with all types of psoriasis and can serve as a diagnostic clue (Figure 1e, see page e2). The differential diagnosis for psoriasis in children depends on the site of involvement. Scalp psoriasis presents with discrete or confluent red patches with silvery scale. The scale may become very thick and mat the hair down in clusters. This is referred to as pityriasis amiantacea (Figure 1a, see page e2). The differential for scalp psoriasis includes: seborrheic dermatitis in infants and adolescents; atopic dermatitis (usually accompanied by other signs, symptoms, or a family history of atopy); and tinea capitis, which should be ruled out with a fungal culture. Plaque and guttate psoriasis may be confused with nummular atopic dermatitis, a form of atopic dermatitis presenting with coin-shaped lesions. This also is typically accompanied by a personal or family history of atopy, and pityriasis rosea, a viral exanthem that follows Langers lines on the skin and thus is distributed in the classic Christmas tree pattern on the trunk and proximal extremities. Diaper pso-

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an individual basis. Counseling for patients with severe psoriasis is appropriate, since adult and preliminary pediatric data show that the risk for comorbidities, especially obesity, hypertriglyceridemia, and hyperglycemia, increases with disease severity.17 TREATMENT Topical Therapy Available topical treatment vehicles include creams, ointments, foams, gels, lotions, liquid solutions, sprays, oils, and drug-impregnated tapes. Thicker vehicles such as ointments (usually petrolatum) are more occlusive and therefore often more effective than creams and lotions. Choice of vehicle is based on the location of the psoriasis and patient preference. Plaques on the extremities call for ointments or creams, whereas hair-bearing sites (scalp) require thinner preparations such as liquids, gels, lotions, sprays, oils, or foams.18

Figure 1. (a) scalp psoriasis; (b) typical plaque psoriasis; (c) guttate psoriasis; (d) diaper psoriasis; (e) nail psoriasis (pits); (f ) adolescent with atrophy and striae after using a highly potent topical steroid (clobetasol) twice daily for 6 months. Source: a-e, Cordoro KM; f, Sugarman J. Reprinted with permission.

riasis must be differentiated from irritant diaper dermatitis (which spares the folds) or candidal diaper dermatitis (beefy red plaques with characteristic satellite papules and pustules).12 ENVIRONMENTAL TRIGGERS A thorough history and physical should be performed to identify potential disease triggers. These include trauma (Koebner phenomenon), infections (especially pharyngeal and perianal group A beta-hemolytic streptococci and viruses including HIV), drugs (particularly recent oral steroid withdrawal), and physical or psychological stress.10 COMORBIDITIES Psoriasis is a chronic inflammatory disease that may not be limited to the skin. Studies in adults have demonstrated an association between psoriasis and metabolic syndrome (hypertension, obesity, dyslipidemia, and hyperglycemia)12 and increased

cardiovascular risk. Psoriasis is also associated with increased rates of depression and decreased quality of life.13 Comorbidities in the pediatric population are less well defined, but data are emerging linking psoriasis to obesity and depression in children.14 Psoriatic arthritis in children is well documented, with a prevalence ranging from 5% to 40%.10,15 Onset age of psoriatic arthritis in children is usually between 9 and 12 years. Severe nail and digital disease is a clinical predictor of joint disease.16 However, correlation between the severity of skin disease and arthritis is usually poor.15 Since the true risk in this population is insufficiently investigated, whether pediatricians and dermatologists should screen youths with psoriasis for the presence of comorbid conditions remains to be established. A reasonable approach is a detailed history and physical examination, with directed investigations performed on

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Twice-daily application is required for maximum effect of most topical medications. The traditional dogma that ointments are more effective must be reconciled with patient preference to select vehicles that the patient will actually apply. Adolescents often object to greasy ointments on the body and prefer creams, lotions, or foams. An effective compromise is to prescribe cosmetically acceptable vehicles for daytime use and reserve oils and ointments for nighttime use. Corticosteroids Topical corticosteroids (TCS) are the rst-line agents for treatment of psoriasis in all age groups and all body sites. They are anti-inammatory, anti-proliferative, and reduce erythema, scaling, and pruritus.19 TCS range in potency from the very weak Class VII to highly potent Class I agents.20 In general, psoriasis on sensitive or occluded sites (face, neck, genitalia/diaper area, folds, exures including axillae and proximal thighs) call for lower potencies, whereas thicker psoriasis on the trunk, extremities, palms, soles, and scalp require higher potencies. The thin skin of the case and inguinal folds is also more at risk for irritation from tazarotene and calcipotriene. Figure 2 provides a quick reference for the potency of TCS that may be used for various body sites. If higher potency agents are required for thicker plaques in high-risk sites such as the diaper area, their use should be limited to short bursts of daily application only until the plaques thin down, followed by reduction of potency, frequency, or both. An often under-appreciated area of concern for the risk of atrophy and striae from long-term use of high-potency topical steroids is the proximal medial aspect of the upper and lower extremities, especially in rapidly growing, peripubertal patients (Figure 1f, see page e2). Extremely potent agents should be

Face/Anogenital: Low-potency TCS TCI 3% LCD (in emollient or 1% HC) Emollient Eyelids: 1% HC ointment or TCI Emollient

Scalp: Low- to high-potency TCS or shampoo Calcipotriene solution Tar/LCD lotion, foam, or shampoo Keratolytics (salicylic acid gel or shampoo; lactic acid, urea) Anthralin Trunk/Extremities: Low- to high-potency TCS Calcipotriene 5% to 20% LCD in low-mid TCS Tazarotene (thick plaques) Keratolytics prn

Palms/Soles: Mid- to high-potency TCS 5% to 20% LCD in TCS Salicylic acid (>6 y/o) Urea 10% to 40% Tazarotene Calcipotriene

TCS: topical corticosteroids HC: hydrocortisone LCD: liquor carbonis detergens Keratolytics: salicylic or lactic acid; urea 10% to 40%

Nails: Tazarotene TCI (esp. for pustular variants) Calcipotriene TCS (beware of digital atrophy) Keratolytics prn

Figure 2. Guide to site-based topical therapy for psoriasis. Source: Cordoro KM. Reprinted with permission.

avoided or used sparingly in infants. To decrease the risk of potential adverse effects, such as cutaneous atrophy, combine or rotate topical steroids with steroid-sparing alternatives, such as vitamin D analogues, coal tar/liquor carbonis detergens (LCD), anthralin, and topical calcineurin inhibitors. Infants have a high ratio of body surface area to mass, thus widespread application of TCS may result in systemic absorption.21 Close supervision and use of combination and rotational therapies will enhance efficacy and minimize the risk of side effects of TCS, such as skin atrophy, striae, telangiectasia, and adrenal suppression. A recent study examined the atrophogenic potential of TCS used for inflammatory skin diseases in children.22 The researchers concluded that, when used appropriately, TCS do not cause skin atrophy.22 Their data provide evidence that the true risk of thinning the skin from the routine use of topical steroids in children is far less than previously thought; however, caution is still advised and patients using topical corticosteroids should be monitored routinely for beneficial as well as adverse effects.

There are a multitude of TCS formulations and potencies (see Table, page e4). For practical purposes, start with a short list of at least one generic medication from each of the potency classes and their available formulations. For example: low potency desonide is available in an ointment, cream, lotion, gel, and foam; mid-potency triamcinolone acetonide is available as an ointment, cream, lotion, solution, and spray; and high-potency clobetasol propionate is available as an ointment, cream, lotion, solution, foam, spray, and shampoo. This clinically useful toolbox of topical corticosteroids will aid in developing a site- and severitybased treatment plan. The patient/family can participate in the care plan by selecting treatment vehicle. Vitamin D Analogues Calcipotriene (calcipotriol in Europe and Canada) and calcitriol are vitamin D3 analogues that play a primary role in the treatment of childhood and adult psoriasis. In the US, calcipotriene is available in an ointment, cream, and solution; calcitriol is available in an ointment. They are efcient non-steroidal alternatives for monotherapy or

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TABLE.

Commonly Used Topical Agents for Pediatric Psoriasis*

Agent Available Concentrations Available Vehicles
Ointment Cream Lotion Gel Foam Ointment Cream Lotion Solution Ointment Cream Solution Gel Foam Spray Shampoo

Low-potency topical corticosteroids

Desonide Used for: sensitive areas (face, axillae, groin)

0.05%

Mid-potency topical corticosteroids

Triamcinolone acetonide

0.025% 0.1% 0.5%

High-potency topical corticosteroids

Clobetasol propionate Limit to short bursts if used in high-risk areas (axillae, groin); then decrease potency

0.05%

Calcipotriene Vitamin D analogue Used in combination with topical corticosteroids for steroid-sparing effect Tazarotene 0.005% Cream Solution (scalp)

Topical retinoid

0.05% 0.1%

Gel

Coal tar/liquor carbons detergens (LCD)

Anti-inammatory and keratolytic; can be compounded with corticosteroids, emollients, lactic and salicylic acids (eg, 5% LCD in 0.1% triamcinolone ointment)

20% LCD 2% crude coal tar (CCT) 5% CCT 10% CCT

Can be compounded in: Petrolatum Aquaphor Nutraderm lotion Cetaphil cream 2% available OTC as foam

*Not a comprehensive summary. Source: Cordoro KM. Reprinted with permission.

in combination with topical steroids.23 Regimens combining vitamin D analogues and topical steroids are well tolerated, steroid-sparing, and synergistic in action.24 Calcipotriene ointment has documented efcacy, tolerability, and safety in children with psoriasis. It can be used as monotherapy in very mild cases with thin patches and plaques or in combination with other topical agents for thicker or more severe disease. Local irritation is the most common side effect.25

Adverse effects on systemic calcium homeostasis in adult psoriasis patients have been evaluated and are related to dose per unit of body weight. Though no formal guidelines exist for children, use of up to 45 g/m2/week of calcipotriene in children does not seem to influence serum ionized calcium levels. Calcitriol ointment has also been shown to be effective and safe in children, with complete clearing of treated plaques after 4 weeks of treatment.26 Calcitriol ointment is report-

edly less irritating than calcipotriene ointment when used in sensitive areas such as flexures.27 Coal Tar and LCD Tar is a safe, effective, steroid-sparing treatment for childhood psoriasis. Crude coal tar has antipsoriatic, antiseborrheic, antipruritic, and keratolytic effects.28 The mechanism of action is largely unknown, but enzyme inhibition, antimitotic actions, and suppression of DNA synthesis have been iden-

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tied.29 Tar is supplied in a variety of topical formulations and shampoos and can be used alone or compounded with corticosteroids, emollients, or lactic and salicylic acids. Coal tar is black and therefore may stain clothing, linens, and skin, potentially resulting in decreased compliance. LCD is a modied coal tar with a cream to yellowish color that has largely replaced crude coal tar in the outpatient setting because of its cosmetic acceptability.30 LCD can be compounded in an ointment, cream, or solution vehicle in concentrations from 0.5% to 20%. The best use of tar is as a keratolytic (induces sloughing of scale), anti-inammatory agent on very thick plaques of psoriasis on the extremities, trunk, palms, soles, and scalp. Side effects of tar may include folliculitis, irritation, and photosensitivity. Tar should not be used on pustular or erythrodermic psoriasis. There is no denitive evidence of increased risk for skin cancer above the baseline incidence for the general population from the use of therapeutic tar.31-33 Tar-based agents create photosensitivity and should be avoided on the face. Tazarotene Tazarotene is a third-generation topical retinoid used to treat plaque psoriasis and moderate to severe acne vulgaris. Similar to other retinoids, tazarotene restores normal epidermal differentiation and proliferation and reduces inammation.34 Tazarotene is neither sensitizing nor phototoxic35 but dose-related skin irritation often necessitates the use of topical steroids applied at the same or different time of day.36 Supplied as a cream or gel in 0.05% and 0.1% concentrations, tazarotene should be limited to thicker plaques on nonintertriginous sites. Irritation can be minimized by starting with 0.05% cream applied for 10 to 60 minutes per day, then washed off (short contact therapy), or applying on alternate days or once weekly. Tazarotene is also effective for nail psoriasis.37,38 Tazarotene is a pregnancy category X agent in the US. Topical Calcineurin Inhibitors Tacrolimus and pimecrolimus are non-steroidal immunomodulating macrolactams that inhibit IL-2 production and T-cell activation and proliferation.39 Both topical calcineurin inhibitors (TCI) are FDA-approved for second-line intermittent treatment of atopic dermatitis in patients aged 2 years and older (pimecrolimus and tacrolimus 0.03%) and 15 years and older (tacrolimus 0.1%). TCIs are used as steroid-sparing options in combination or rotation with other topicals for psoriasis at high-risk sites for adverse effects of long-term topical steroid use (face, eyelids, exures, ngertips/ nails, anogenital region). Stinging or burning may occur when TCIs are applied to ssured plaques or thin skin such as the eyelids. TCIs have not been proven unequivocally effective for thick plaque psoriasis on the elbows, knees, or trunk. Anthralin Anthralin (dithranol) is a potent anti-inflammatory and antiproliferative agent.40 It is a synthetic version of chrysarobin, a natural substance derived from the araroba tree of South America, which has been used to treat psoriasis for nearly 100 years.41 Negligible systemic absorption is responsible for anthralins excellent safety profile. Its use is limited because of the potential for staining and irritation with prolonged skin contact times. However, short contact and minutes therapy are popular alternatives (increasing concentrations 0.1% to 3% dithranol applied to the skin and left in place for 10 to 30 minutes daily until slight irritation develops, then maintain the same dose/time until clear).42 Lower concentrations or shorter contact time should be used on more sensitive sites such as anogenital skin. Salicylic Acid, Lactic Acid, Urea Keratolytics are peeling agents used to debulk thick plaques of psoriasis and are used in combination regimens with anti-inammatory topicals such as TCS and vitamin D analogues. Salicylic acid, available over-the-counter (OTC) as a shampoo and by prescription as a 6% gel, is a useful adjunctive keratolytic for thick, localized plaques on the scalp, palms, and soles. It should be avoided in infants because of the risk for percutaneous salicylism.43 Lactic acid and urea are also effective keratolytics available OTC and by prescription as creams, lotions, and ointments. PHOTOTHERAPY AND SYSTEMIC THERAPY Although most cases of psoriasis can be managed adequately with topical therapies, a subset of children present with severe or rapidly evolving disease that may warrant the use of systemic or phototherapy. Phototherapy is an effective treatment for carefully selected patients with diffuse guttate or plaque psoriasis or focal debilitating palmoplantar psoriasis. Three main types of therapeutic light options exist: broadband UVB; narrowband UVB; and UVA. Narrowband UVB is often selected for treating children because of its ease of use and safety. Phototherapy is administered in a physicians office or phototherapy center and rarely via home phototherapy units. Short-term adverse reactions include burn and itch, while potential long-term risks include photodamage and cutaneous carcinogenesis.44,45 Severe or refractory plaque, pustular, or erythrodermic psoriasis and psoriatic arthropathy require systemic

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therapy. The three most commonly used systemic treatments for psoriasis in children are: acitretin, a non-immunosuppressing systemic retinoid; and the immunosuppressants methotrexate and cyclosporine. Because they have not undergone the scrutiny of randomized controlled trials in this population, none are FDA-labeled for psoriasis in children. Accumulated data regarding the utility, benets, and risks of these agents for treatment of psoriasis derives largely from long-term use in children with other disorders such as ichthyoses (acitretin), juvenile rheumatoid arthritis (methotrexate), and organ transplantation (cyclosporine). There are vast amounts of anecdotal data regarding the use of these medications in pediatric psoriasis; however, formalized treatment and monitoring guidelines do not yet exist. Patient selection is critical and requires expert dermatologic consultation. Targeted therapy, rather than generalized immunosuppression, represents the newest direction in treatment and is accomplished by use of biologic molecules. Tumor necrosis factor alphainhibitors (etanercept, adalimumab, and iniximab) are the most commonly used. Of all the currently available biologics, etanercept has the most signicant published literature to substantiate recommendations for its use in the pediatric psoriasis population.46 Although biologics appear to be generally safe and effective, long-term data for psoriasis are lacking; serious adverse events, including opportunistic infections, have been reported. Careful consideration of the risk-benet ratio for individual patients is required when deciding whether to use this class of medications, which is very expensive. CONCLUSION Managing children with psoriasis can be challenging due to the lack of approved therapies and compliance issues. In contrast to adults with psoriasis, little is known about the potential comorbidities of pediatric psoriasis. Given the potential effect of this disease on overall physical and emotional well-being, these patients require vigilant monitoring. Although a subset of children present with severe, rapidly evolving disease that requires systemic or phototherapy, most cases are mild, adequately managed with topical preparations. In patients with severe or refractory disease, or for psoriasis accompanied by comorbidities such as obesity or arthritis, timely referral for dermatologic consultation may lessen the potential effect of psoriasis on patients and families. REFERENCES
1. Gelfand JM, Weinstein R, Porter SB, Neimann AL, Berlin JA, Margolis DJ. Prevalence and treatment of psoriasis in the United Kingdom: a population-based study. Arch Dermatol. 2005;141(12):1537-1541. 2. Christophers E. Psoriasis epidemiology and clinical spectrum. Clin Exp Dermatol. 2001;26(4):314-320. 3. Stern RS, Nijsten T, Feldman SR, Margolis DJ, Rolstad T. Psoriasis is common, carries a substantial burden even when not extensive, and is associated with widespread treatment dissatisfaction. J Investig Dermatol Symp Proc. 2004;9(2):136-139. 4. Tollefson MM, Crowson CS, McEvoy MT, Maradit Kremers H. Incidence of psoriasis in children: a population-based study. J Am Acad Dermatol. 2010;62(6):979-987. 5. Raychaudhuri SP, Gross J. A comparative study of pediatric onset psoriasis with adult onset psoriasis. Pediatr Dermatol. 2000;17(3):174-178. 6. Rogers M. Childhood psoriasis. Curr Opin Pediatr. 2002;14(4):404-409. 7. Farber EM, Nall ML. The natural history of psoriasis in 5,600 patients. Dermatologica. 1974;148(1):1-18. 8. Morris A, Rogers M, Fischer G, Williams K. Childhood psoriasis: a clinical review of 1,262 cases. Pediatr Dermatol. 2001;18(3):188-198. 9. Burden AD. Management of psoriasis in childhood. Clin Exp Dermatol. 1999;24(5):341-345. 10. Cordoro KM. Management of childhood psoriasis. Adv Dermatol. 2008;24:125-169. 11. Telfer NR, Chalmers RJ, Whale K, Colman G. The role of streptococcal infection in the initiation of guttate psoriasis. Arch Dermatol. 1992;128(1):39-42. 12. Silverberg NB. Pediatric psoriasis: an update. Ther Clin Risk Manag. 2009;5:849-856. 13. Kimball AB, Gladman D, Gelfand JM, et al. National Psoriasis Foundation clinical consensus on psoriasis comorbidities and recommendations for screening. J Am Acad Dermatol. 2008;58(6):1031-1042. 14. Rapp SR, Feldman SR, Exum ML, Fleischer AB, Jr., Reboussin DM. Psoriasis causes as much disability as other major medical diseases. J Am Acad Dermatol. 1999;41(3 Pt 1):401-407. 15. Augustin M, Glaeske G, Radtke MA, Christophers E, Reich K, Schafer I. Epidemiology and comorbidity of psoriasis in children. Br J Dermatol. 2010;162(3):633-636. 16. Gottlieb A, Korman NJ, Gordon KB, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 2. Psoriatic arthritis: overview and guidelines of care for treatment with an emphasis on the biologics. J Am Acad Dermatol. 2008;58(5):851-864. 17. Stoll ML, Lio P, Sundel RP, Nigrovic PA. Comparison of Vancouver and International League of Associations for rheumatology classication criteria for juvenile psoriatic arthritis. Arthritis Rheum. 2008;59(1):51-58. 18. Mahoney A. The severity of pediatric psoriasis correlates with the risk of obesity: An international multicenter controlled assessment. Paper presented at: SID 2011; Abstract 215.2011. 19. Feldman SR. Approaching psoriasis differently: patient-physician relationships, patient education and choosing the right topical vehicle. J Drugs Dermatol. 2010;9(8):908-911. 20. Leman J, Burden D. Psoriasis in children: a guide to its diagnosis and management. Paediatr Drugs. 2001;3(9):673-680. 21. Cornell RC, Stoughton RB. Correlation of the vasoconstriction assay and clinical activity in psoriasis. Arch Dermatol. 1985;121(1):63-67. 22. Maibach HI, Wester RC. Issues in measuring percutaneous absorption of topical corticosteroids. Int J Dermatol. 1992;31 Suppl 1:21-25. 23. Hong E, Smith S, Fischer G. Evaluation of the atrophogenic potential of topical corticosteroids in pediatric dermatology patients. Pediatr Dermatol. 2011;28(4):393-396. 24. Koo JY. New developments in topical sequential therapy for psoriasis. Skin Therapy Lett. 2005;10(9):1-4. 25. Lebwohl M, Siskin SB, Epinette W, et al. A multicenter trial of calcipotriene ointment and halobetasol ointment compared with either agent alone for the treatment of psoriasis. J Am Acad Dermatol. 1996;35(2 Pt 1):268-269. 26. Darley CR, Cunliffe WJ, Green CM, Hutchinson PE, Klaber MR, Downes N. Safety and efcacy of calcipotriol ointment (Dovonex) in treating children with psoriasis vulgaris. Br J Dermatol. 1996;135(3):390-393. 27. Saggese G, Federico G, Battini R. Topical application of 1,25-dihydroxyvitamin D3 (calcitriol) is an effective and reliable therapy to cure skin lesions in psoriatic children. Eur J

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Pediatr. 1993;152(5):389-392. 28. Zhu X, Wang B, Zhao G, et al. An investigator-masked comparison of the efficacy and safety of twice daily applications of calcitriol 3 microg/g ointment vs. calcipotriol 50 microg/g ointment in subjects with mild to moderate chronic plaque-type psoriasis. J Eur Acad Dermatol Venereol. 2007;21(4):466-472. 29. Cram DL. Psoriasis: treatment with a tar gel. Cutis. 1976;17(6):1197-1198, 1202-1203. 30. Farber EM, Nall L. Psoriasis. A review of recent advances in treatment. Drugs. 1984;28(4):324-346. 31. Lin AN, Moses K. Tar revisited. Int J Dermatol. 1985;24(4):216-218. 32. van Schooten FJ, Godschalk R. Coal tar therapy. Is it carcinogenic? Drug Saf. 1996;15(6):374-377. 33. Pittelkow MR, Perry HO, Muller SA, Maughan WZ, OBrien PC. Skin cancer in patients with psoriasis treated with coal tar. A 25-year follow-up study. Arch Dermatol. 1981;117(8):465-468. 34. Pion IA, Koenig, KL, Lim, HW. Is dermatologic usage of coal tar carcinogenic? A review of the literaure. Dermatol Surg. 1995;21(3):227-231. Esgleyes-Ribot T, Chandraratna RA, Lew-Kaya DA, Sefton J, Duvic M. Response of psoriasis to a new topical retinoid, AGN 190168. J Am Acad Dermatol. 1994;30(4):581-590. Marks R. Early clinical development of tazarotene. Br J Dermatol. 1996;135 Suppl 49:26-31. Lebwohl MG, Breneman DL, Goffe BS, et al. Tazarotene 0.1% gel plus corticosteroid cream in the treatment of plaque psoriasis. J Am Acad Dermatol. 1998;39(4 Pt 1):590-596. Bianchi L, Soda R, Diluvio L, Chimenti S. Tazarotene 0.1% gel for psoriasis of the ngernails and toenails: an open, prospective study. Br J Dermatol. 2003;149(1):207-209. Diluvio L, Campione E, Paterno EJ, Mordenti C, El Hachem M, Chimenti S. Childhood nail psoriasis: a useful treatment with tazarotene 0.05%. Pediatr Dermatol. 2007;24(3):332-333. Nghiem P, Pearson G, Langley RG. Tacrolimus and pimecrolimus: from clever prokaryotes to inhibiting calcineurin and treating atopic dermatitis. J Am Acad Dermatol. 2002;46(2):228-241. Reichert U, Jacques Y, Grangeret M, Schmidt R. Antirespiratory and antiproliferative activity of anthralin in cultured human keratinocytes. J Invest Dermatol. 1985;84(2):130-134. Ashton RE, Andre P, Lowe NJ, Whiteeld M. Anthralin: historical and current perspectives. J Am Acad Dermatol. 1983;9(2):173-192. Runne U, Kunze J. Short-duration (minutes) therapy with dithranol for psoriasis: a new out-patient regimen. Br J Dermatol. 1982;106(2):135-139. Zeichner JA, Lebwohl MG, Menter A, et al. Optimizing topical therapies for treating psoriasis: a consensus conference. Cutis. 2010;86(3 Suppl):5-31; quiz 32. Diffey BL, Farr PM. The challenge of followup in narrowband ultraviolet B phototherapy. Br J Dermatol. 2007;157(2):344-349. Wolff K. Side-effects of psoralen photochemotherapy (PUVA). Br J Dermatol. 1990;122 Suppl 36:117-125.

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