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Topical : back to basics

Topical corticosteroids are among the most commonly required, should be limited to the lowest effective Nancy P Lee prescribed in the ambulatory setting.1 They strength.5 Edgar R Arriola a wide variety of der- Drug Information are the cornerstones of therapy for Center matoses, such as atopic dermatitis, contact dermatitis, pso- Vehicle Department of riasis, seborrheic dermatitis, and intertrigo.2'3 In addition, Pharmaceutical Services depends on the type oflesion and they may also serve as adjuvant or alternative therapy for The selection ofvehide UCLA Medical Center anatomic region that is affected. Most topical cortico- Los Angeles, CA 90095 various other inflammatory, hyperproliferative and pru- the are available in many formulations, induding the clinical effects of to: ritic conditions. It is thought that ointment, cream, lotion, gel, solution, and aerosol. In ad- Correspondence anti- Dr Arriola topical corticosteroids are mediated by their dition to being a carrier for the active drug, the vehide inflammatory, vasoconstrictive, anti-proliferative, and im- [email protected] may function to hydrate the skin and augment drug pen- edu munosuppressive properties. etration. Ointments, which consist of oleaginous bases such as petrolatum, provide hydration to the stratum comeum by WHAT SHOULD BE CONSIDERED IN THE acting as an occlusive barrier. Penetration of the active SELECTION OF TOPICAL CORTICOSTEROIDS? agent is therefore enhanced, resulting in improved po- A myriad oftopical products is available for tency. Ointments are ideal for the management of dry, the management ofdermatoses. A basic understanding of scaly or lichenified lesions and on areas with thick skin, several key factors should help clinicians select appropriate such as the palms and soles. Emollient creams, which are preparations that maximize therapeutic efficacy yet mini- creams that contain an increased amount of petrolatum, mize the potential for adverse effects. are less greasy and may be more cosmetically appealing to In addition to evaluating the relative potency of the patients than ointments. In general, most creams, lotions active agent, clinicians should consider factors that modu- and gels are water based and do not significantly provide late the dinical efficacy of the selected agent, such as the hydration to the skin. These nonocclusive vehides are choice ofvehicle, the affected application site, and the use preferable for weeping lesions and for application on hairy of occlusive dressing. areas and flexures. (Note: some preparations are now for- mulated with an optimized vehide, resulting in equal po- tency for ointment, cream, and/or gel formulations.) Potency Since the introduction of topical in the 1950s, various topical corticosteroids have been developed Application site to improve the degree of potency. In particular, chemical Absorption oftopical corticosteroids differs at various ana- alterations to the active moeity such as halogenation or tomic sites. Areas with thick stratum comeum, such as the esterification have produced intrinsically more potent soles of the feet or palms of the hand, allow for minimal agents. Topical corticosteroid preparations are categorized penetration. Consequently, high potency preparations according to their relative potency as determined by va- may be required on these areas to ensure a clinical re- socontrictive assays (Table 1). Keep in mind, however, the sponse. Areas such as the scrotum, parts ofthe face (eyelids vasoconstrictive activity may not always correlate with in particular), and intertriginous regions permit rapid and therapeutic efficacy.4 extensive drug penetration due to thinner stratum cor- The selection of potency should be based on the re- neum. These areas are therefore more susceptible to sponsiveness of the dermatologic condition. Highly re- adverse effects. The use of low potency preparations is sponsive dermatosis, such as intertriginous or generally preferred in these areas, although recalcitrant atopic dermatitis, should be treated with weak corticoste- conditions (for example, discoid lupus erythematosus and roid preparations, whereas less responsive or recalcitrant lichen sclerosis) may require higher potency preparations.4 conditions (for example, palmoplantar or nail psoriasis, Another consideration is the extent of skin involve- lupus erythematosus) often require higher potency ment requiring topical corticosteroid therapy. Because of agents.3 When a high potency agent is selected initially to increased risk ofsystemic absorption, low to medium po- control and arrest the dermatosis, maintenance therapy, if tency preparations are preferable when treating large sur-

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Table s

Group I (Most Potent) dipropionate Diprolene', Diprolene0 AF 0.05% Cream, ointment, or gel (optimized vehicle) propionate Temovate0 o.os% Cream or ointment diacetate Psorcons o.o0% Ointment (optimized vehicle) Group 11 Cyclocort0 0.1% Ointment Betamethasone dipropionate Diprosones o.o05% Ointment Topicorts 0.25% Cream or ointment Desoximetasone Topicort' o.os% Gel Diflorasone diacetate Florone', Maxiflor o.os% Ointment Lidex' o.os% Cream, ointment, or gel Halogr O.I% Cream ...... Group III Betamethasone diproprionate Diprosone' o.o0% Cream Valisone' o.1% Ointment Diftorasone diacetate FloroneO, Maxiftors o.os% Cream furoate Elocon' o.i% Ointment acetonide Aristocort' o.s% Cream

...... Group IV Desolxmetasone Topicort' LP o.o5% Cream acetonide Synalar" HP 0.2% Cream Synalar' 0.025% Ointment Flurandrenolide Cordran' 0.05% Ointment Triamcinotone acetonide Aristocort*, Kenalog' o.i% Ointment

...... Group V Betametasone dipropinate Diprosone' o.o0% Lotion Betametasone valerate Valisone's o.1% Cream, lotion Fluocinolone acetonide Synalar' 0.025% Cream Flurandrenolide Cordran' o.os% Cream Locoid' 0.1% Cream Westcort' 0.2% Cream Dermatop' o.i% Cream Kenalog' 0.1% Cream, lotion

...... Group VI diproprionate Aclovate' o.os% Cream, ointment Tridesilon' o.os% Cream Fluocinolone acetonide Synalar' o.oi% Solution

Note: Group I represents the super-potent category; potency descends with each group; Group VIl consist ofweak topical corticosteroids such as hydrocortisone, , , and .

face areas.4 The integrity ofthe epidermal area should also daily applications have been recommended.5'7 Recent un- be evaluated when selecting a preparation to avoid exces- derstanding ofdrug penetration and deposition, however, sive percutaneous corticosteroid absorption. suggests less frequent application may be more appropriate owing to the depot effect of the skin. Less frequent appli- Occlusive dressings cation also offers the advantages of reducing the develop- The use of occlusive dressing to enhance drug potency is ment ofside effects and tachyphylaxis, improving patient less common because of the availability of super potent compliance, and reducing the cost of therapy.7 topical corticosteroids. Application of occlusive dressings, General guidelines developed by American Academy however, such as plastic wraps and hydrocolloid dressings, ofDermatology advise once or twice daily applications for remains an effective method when treating localized, re- most topical corticosteroid preparations. Skin with thick calcitrant conditions. The permeability of the drug under stratum corneum from which the is easily re- ocdusive dressing may be increased up to 10-fold.6 moved may require more frequent application; intermit- tent and intermittent scheduling (for example, every other WHAT IS THE OPTIMAL FREQUENCY day, weekends only) may be effective for chronic condi- OF APPLICATION? tions requiring maintenance therapy.4 Daily application The frequency of application varies with the preparation of nonmedicated emollient creams or ointments may be selected and the condition treated. Traditionally, multiple substituted during the drug-free intervals.6

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WHAT ARE THE POTENTIAL ADVERSE EFFECTS WHAT SPECIAL PRECAUTIONS SHOULD OF TOPICAL CORTICOSTEROID THERAPY? BE CONSIDERED IN PEDIATRIC AND Systemic adverse effects GERIATRIC PATIENTS? A major concern associated with topical corticosteroid Pediatric patients, in particularly infants, may be more therapy is the risk of systemic absorption. Although they susceptible to the side effects oftopical steroids due to their are rare, systemic complications have manifested as a result greater skin surface area-to-body weight ratio and fragile of topic topical corticosteroid use, such as suppression of skin.3"' The most common indication for topical corti- the hypothalamic-pituitary-adrenal axis suppression, costeroids in infants and children is atopic eczema. The Cushing's syndrome, hyperglycemia, growth suppression use of 1% hydrocortisone is usually sufficient, although a in children, and femoral head osteonecrosis.5'8 stronger preparation may be indicated for a limited dura- Physicians should always keep in mind the conditions tion during exacerbations." The use ofhigh-potency cor- that potentiate the risk for systemic absorption: use ofhigh ticosteroids should generally be avoided in children. Keep potency preparations of high potency, treatment for pro- in mind, occlusive coverings, such as diapers or tight cloth- longed duration, application over large surface areas, ad- ing, may inadvertently increase percutaneous absorption. dition of occlusive dressing, and use on areas with Geriatric patients, especially those with existing age-related perturbed skinperturbed skin barrier function. Periodic skin atrophy, are also at increased risk for side effects from dinical and laboratory testing may be indicated ifthe drug topical corticosteroids.3 Similar precautions should be is to be used for long periods and/or on large areas of the taken when prescribing for elderly patients. body.2 If suppression of the hypothalamic-pituitary- adrenal axis is detected, slow weaning of the topical cor- CONCLUSION ticosteroid, reduction ofapplication frequency, or titration As with any prescribed treatment, patient education is to a lower potency preparation is recommended. essential in optimizing therapy. Patients should be in- structed regarding the specific amount of topical cortico- to use as well as the proper application techniques. Local adverse effects They should also be cautioned against the occlusion of Local adverse effects, in contrast, are encountered more treated area with bandages, dressings, or any other cover- frequently and have become more prevalent with the in- ings unless specifically directed by the physician. Although troduction of high potency topical corticosteroids. These topical corticosteroids are frequently used without any un- effects indude epidermal and dermal atrophy, striae, pur- toward effects, the perils ofunregulated use should be kept pura, telangiectasia, acneiform eruptions and rosacea. Lo- in mind, especially with the availability of newer, super- cal hypertrichosis and hypopigmentation may also occur. potent topical corticosteroids. Although cutaneous adverse effects are generally reversible when treatment is discontinuedupon discontinuation of treatment, atrophic striae may be permanent. Therefore, ...... the use ofhigh potency preparations on delicate areas such References 1 Stem R The pattern of topical corticosteroid prescribing in the United as the face should be avoided due to higher risk of local States, 1989-1991. J Am Acad Dermatol 1996:183-196. reactions. 2 Giannotti B, Pimpinelli N. Topical corticosteroids: which drug and Rebound is a rare adverse effect that may occur after when? Drugs 1992;44:65-71. 3 Baumann L, Kerdel F. Topical . In: Fitzpatrick T, ed. using potent topical corticosteroids. Severe exacerbation of Dermatology in general medicine, 5th ed. New York. McGraw Hill, the dermatosis may ensue as a result ofabrupt discontinu- 1999:2713-2717. 4 Drake L, Dinehart S, Farmer E, et al. Guidelines of care for the use of ation.2'5 Rebound erythema may also occur; the discon- topical glucocorticosteroids. J Am Acad Dermatol 1996:615-619. tinuation of topical corticosteroids, which initially cause 5 Katz H. Topical corticosteroids. Dermatol Clin 1995;13:805-815. 6 Giannotti B. Current treatment guidelines for topical corticosteroids. vasoconstriction, is followed by develop as a result of ex- Drugs 36:9-14. cessive vasodilation when the dmg is withdrawn.9 7 Lagos B, Maibach H. Frequency of application of topical Allergic contact dermatitis to topical corticosteroids corticosteroids: an overview. Br J Dermatol 1998;1 39:763-766. 8 Gilbertson E, Speilman M, Piacquadio D, et al. Super potent topical may also develop and should be considered in patients corticosteroid use associated with adrenal suppression: clinical with dermatitis that is resistant to therapy. Various com- considerations. J Am Acad Dermatol 1998;318-321. 9 Fisher D. Adverse effects of topical corticosteroid use. West J Med ponents ofthe preparation (for example, propylene glycol, 1995;162:123-126. benzyl alcohol) are common sensitizers.3 Hypersensitivity 10 Lutz M, El-Azhary R Allergic contact dermatitis due to topical to the active steroid moiety itself is also frequentlyhas also application of corticosteroids: review and clinical implications. Mayo Clinic Proc 1997;72:1141-1144. been recognized."0 Clinicians should note that cross- 11 Harper J. Topical corticosteroids for skin disorders in infants and reactivity to other structurally related corticosteroid corti- children. Drugs 1998;36(Suppl 5):34-37. 12 McEvoy G, ed. American Hospital Formulary Service drug costeroid compounds that are structurally related may oc- information. Bethesda: American Society of Health-System Pharmacists, cur.'0 1999.

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