This report reflects the best data available atthe time the report was prepared, but caution should be exercisedin interpreting the data; the results of future studies mayrequire alteration of the conclusions or recommendations setforth in this report.

Reprint requests: American Academy ofDermatology, P.O. Box 4014,
Schaumburg, IL 60168-4014. (Provided free of charge)
J AM ACAD DERMATOL1996;35:615-9.
Copyright 1996 by the American Academy of Dermatology, Inc.

Guidelines of care for the use of topicalglucocorticosteroids

Guidelines/OutcomesCommittee: Lynn A. Drake, MD, Chairman, Scott M. Dinehart,MD, Evan R. Farmer, MD, Robert W. Goltz, MD, Gloria F. Graham,MD, Maria K. Hordinsky, MD, Charles W. Lewis, MD, David M. Pariser, MD, Stephen B. Webster, MD, Duane C. Whitaker, MD,Barbara Butler, CPA-SDR Consultant, and Barbara J. Lowery, MPH

Task Force:Sharon A. Raimer, MD, Chairman, Bernice R. Krafchik, MD, EliseOlsen, MD, and William L. Weston, MD

I. Introduction

The American Academy of Dermatology’s Guidelines/Outcomes Committee is developing guidelines of care for our profession. The development of guidelines will promote the continued delivery of quality care and assist those outside our profession in understanding the complexities and scope of care provided by dermatologists. For the benefit of members of the American Academy of Dermatology who practice in countries outside the jurisdiction of the United States, the listed treatments may include agents that are not currently approved by the U.S. Food and Drug Administration.

II. Definition

Topical glucocorticosteroids (corticosteroids) are compounds formulated for application to the skin and mucous membranes. The hydrocortisone molecule or synthetic analogs of hydrocortisone have been modified by halogenation, methylation, acetylation, esterification, and/or double-band induction to increase the therapeutic effect and reduce side effects.

III. Rationale

A. Scope

Millions of people are affected annually with skin diseases that cause marked discomfort, significant morbidity, and rarely death. When skin diseases are extensive or apparent to others, social isolation and difficulty in finding employment may occur. Since the early 1950s, when hydrocortisone cream was found to be an effective antiinflammatory agent, topical corticosteroids have become a mainstay of dermatologic therapy.

Skin diseases amenable to the effects of topical corticosteroids are usually characterized by inflammation, hyperproliferation, and/or immunologic phenomenon. Topical corticosteroids may also be effective in the treatment of skin symptoms, such as burning and pruritus.

B. Issue

Topical corticosteroids have been used extensively worldwide for the past four decades, resulting in the amelioration of skin disease with very few reports of adverse effects. During this time, products with increased efficacy and accompanying increased potential for adverse effects have been developed. Factors that increase clinical efficacy include enhancement of pharmacologic activity of the compound by altering molecular structure, increasing stratum corneum penetration of the compound, and increasing bioavailability of the compound from the vehicle. At present, attempts are being made to engineer compounds that are locally potent but are rapidly metabolized or otherwise designed to have less potential to cause harmful effects.

The vasoconstrictor assay has been the primary method used for classifying the strength of topical corticosteroid preparations and categorizing topical corticosteroids into general groups according to strength. In this document, corticosteroids are grouped as low, medium, high, and very high strength. The vasoconstrictive ability of various preparations does not always correlate with clinical efficacy.

Generic formulations may not be clinically equivalent to brand name products and differences in vehicles may affect the penetration and bioavailability of the product. Topical corticosteroids in an ointment vehicle are generally more potent than the same concentration of the corticosteroid in a cream or lotion vehicle. In addition, stratum corneum penetration and thus efficacy is enhanced by heat, hydration, and/or occlusion and increased when the skin is abraded or inflamed.

Physicians' knowledge of the strength of the corticosteroid to be used and the factors that influence skin penetration should minimize the potential for adverse effects from the application of these compounds.

IV. Diagnostic criteria

Perform history, physical examination, and diagnostic tests as appropriate to establish a diagnosis.

V. Recommendations

Treatment

Medical

Selection criteria for topical corticosteroids

The selection of the topical corticosteroid in terms of strength and vehicle depends on the nature, location, and extent of skin lesion(s), the age of the patient, and the duration of treatment.

Vehicle considerations

Ointments

An ointment is generally the most effective vehicle for treating thick, fissured, lichenified skin lesions. The occlusive nature of the vehicle enhances corticosteroid penetration. Patients may consider ointments aesthetically undesirable.

b) Creams

Creams are generally the vehicle of choice for acute and subacute dermatoses. They may be used on moist skin and in intertriginous areas and are generally aesthetically acceptable to patients. Cream vehicles may be drying, and some patients may benefit from the application of a moisturizer in addition to a corticosteroid cream. Creams require preservatives that may be sensitizing.

c) Solutions, gels, and sprays

Solutions, gels, and sprays are the most aesthetically elegant vehicles for use on the scalp. They also may be useful when, for aesthetic or medical reasons, a non-oil-based vehicle is desirable. These vehicles frequently contain alcohol and propylene glycol that may cause irritation or burning if applied to acute dermatoses, erosions, or fissures.

Nature of skin lesion(s) being treated

Thin, acute, inflammatory skin lesions frequently respond to low- to medium-strength topical corticosteroids.

Chronic, hyperkeratotic, lichenified, or indurated lesions may respond only to high- or very high-strength topical corticosteroid preparations

Location of the skin lesion(s)

Treatment of the face and intertriginous areas (axilla, groin, perineum, and inframammary area) Because of the thin stratum corneum and possibly because of the nature of the pilosebaceous structures in the area, the face is particularly susceptible to local side effects. In intertriginous areas, heat, moisture, a thin stratum corneum, and self-occlusion enhance the penetration of topical corticosteroids that can cause both local side effects and potential systemic effects from the enhanced absorption. The occlusive effect of diapers enhance penetration in the groin area to an even greater extent.

(1) Low-strength preparations are preferred for the face and intertriginous areas.

(2) Short-term (generally 2 weeks) use of more potent agents is occasionally required. These agents should rarely, if ever, be used in the diaper area of infants.

(3) Recalcitrant lesions of the face or intertriginous areas such as those of discoid lupus erythematosus and lichen sclerosus may require more potent corticosteroids or a longer duration of treatment.

Lesions on skin with a thick stratum corneum, such as the palms and soles, frequently require treatment with high- or very-high strength topical corticosteroids to achieve significant improvement.

Extent of the body surface area to which the corticosteroid is to be applied

Because of the likelihood of systemic absorption, corticosteroids of low to medium strength are preferred when large areas are to be treated.

5) Age

Age is a consideration in selection, particularly in children and elderly patients, because of the body surface area to weight ration in infants, and the thinness and fragility of the skin of premature infants and the elderly.

6) Duration of treatment

a) Whenever possible, the duration of daily use of very-high-strength topical corticosteroids should not exceed 3 weeks. Recalcitrant lesions on small body surface areas may be treated for a longer duration of time.

b) Medium- and high-strength topical corticosteroids rarely cause side effects when used for 3 months or less. Exceptions include use on the face and in intertriginous areas. For treatment of longer duration, intermittent therapy may be preferable to long-term continuous therapy.

c) Side effects are rare with the use of low-strength topical corticosteroids. However, even with these agents, intermittent therapy may be preferred to continuous therapy for long-term management of chronic skin diseases, particularly if large surface areas are being treated.

d) Topical corticosteroids should be discontinued when the skin disease has resolved. Long-term therapy with topical corticosteroids may be used for a chronic skin disease that is responding to treatment with the medication. If continuous long-term treatment is needed, patients should be monitored for the development of side effects and tachyphylaxis (loss of clinical effect over time).

Frequency of application

The recommended frequency of application varies depending on the topical corticosteroid selected and the site to be treated.

Once- or twice-daily applications are usually recommended for most preparations. Occasionally, more frequent application is necessary.

Skin with a thick stratum corneum and from which the medication is easily removed during normal activity, such as the palms and soles, may require more frequent application.

Other regimens, such as every-other-day therapy or weekend-only (pulse therapy) application, may be effective for chronic conditions in selected cases.

Special considerations

Use the lowest potency corticosteroid that is effective, especially on infants and children.

Use of topical corticosteroids under plastic wrap, tight-fitting clothing, or under diapers may increase absorption several fold.

Prolonged use should be avoided in the periorbital area, face, and intertriginous areas.

Use in pregnancy

Topical corticosteroids may cause fetal abnormalities in animals if used in large amounts, with occlusive dressing, for prolonged periods of time, or if the more potent agents are used, but fetal abnormalities have not been documented in human beings.

5) Breast-feeding

It is not known whether topical corticosteroids are excreted in breast milk.

No adverse effects on lactation from the use of topical corticosteroids have been documented in human beings.

Topical corticosteroids should not be applied to the nipples before nursing.

Other

Reported side effects of topical corticosteroid use may include

1) Cutaneous and/or local effects

Acneiform eruption, including folliculitis, rosacea

Periocular and perioral dermatitis

Atrophy of the epidermis and dermis, skin fragility (elderly or sun-damaged skin, intertriginous areas, and the face are most susceptible)

Delayed wound healing

Gluteal granulomas

Purpura

Portugal hotelsTelangiectases and erythema

Striae

Hypopigmentation

Hypertrichosis

Masking or aggravation of dermatophyte infection

Secondary infection or aggravation of existing infection

Contact dermatitis

(1) May be due to preservatives or other ingredients of the vehicle

(2) May be due to corticosteroid molecule, in which case may cross-react with corticosteroid molecules of similar structure

n) Other

Systemic side effects

Seen most frequently from prolonged and extensive use in children or with the use of very-high-strength topical corticosteroid compounds

Cataracts, glaucoma with periorbital use

Adrenal suppression (hypothalamic-pituitary-adrenal axis)

Growth retardation (infants and young children)

(1) Catch-up growth expected when corticosteroid use discontinued

(2) Continuous long-term treatment near puberty should be avoided. If growth is suppressed during what would normally be prepubertal growth spurt, epiphyses may close during puberty before catch-up growth can occur.

d) Hypertension

e) Cushing's syndrome

f) Other

Surgical

Not applicable

3. Other

Not applicable

Miscellaneous

Not applicable

VI. Supportingevidence

See Bibliography(Appendix)

VI. Disclaimer

Adherence to these guidelines will not ensure successful treatment in every situation. Further, these guidelines should not be deemed inclusive of all proper methods of care or exclusive of other methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding the propriety of any specific procedure must be made by the physician in light of all the circumstances presented by the individual patient. For the benefit of members of the American Academy of Dermatology who practice in countries outside the jurisdiction of the United States, the listed treatments may include agents that are not currently approved by the U. S. Food and Drug Administration.

Appendix. Bibliography

Barry BW, Woodford R. Comparative bioavailability and activity of proprietary topical corticosteroid preparations: vasoconstrictor assays on thirty-one ointments. Br J Dermatol 1975;93:563-71.

Barry BW, Woodford R. Comparative bioavailability of proprietary topical corticosteroid preparations: vasoconstrictor assays on thirty creams and gels. Br J Dermatol 1974;91:323-38.

Bartorelli A, Rimondini A. Severe hypertension in childhood due to prolonged skin application of a mineralocorticoid ointment. Hypertension 1984;6:586-8.

Becker B. Cataracts and topical corticosteroids. Am J Ophthalmol 1964;58:872-3.

Becker B. The effect of topical corticosteroids in secondary glaucomas. Arch Ophthalmol 1964;72:769-71.

Bode HH. Dwarfism following long-term topical corticosteroid therapy. JAMA 1980;244:813-4.

Brattsand R, Thalen A, Roempke K, et al. Influence of 16 alpha, 17 alpha-acetal substitution and steroid nucleus fluorination on the topical to systemic activity ratio of glucocorticoids. J Steroid Biochem 1982;16:779-86.

Bucks DA, McMaster JR, Maibach HI, et al. Bioavailability of topically administered steroids: a mass balance technique. J Invest Dermatol 1988;91:29-33.

Cornell RC. Clinical trials of topical corticosteroids in psoriasis: correlations with the vasoconstrictor assay. Int J Dermatol 1992;31:38-40.

Cornell RC, Stoughton RB. Correlation of the vasoconstriction assay and clinical activity in psoriasis. Arch Dermatol 1985;121:63-7.

Curtis JA, Cormode E, Laski B, et al. Endocrine complications of topical and intralesional corticosteroid therapy. Arch Dis Child 1982;57:204-7.

Goette DK, Odom RB. Adverse effects of corticosteroids. Cutis 1979;23:477-87.

Guin JD. Contact sensitivity to topical corticosteroids. J Am Acad Dermatol 1984;10:773-82.

Hepburn D, Yohn JJ, Weston WL. Topical steroid treatment in infants, children and adolescents. Adv Dermatol 1994;9:225-54.

Jackson DB, Thompson C, McCormack JR, et al. Bioequivalence (bioavailability) of generic topical corticosteroids. J Am Acad Dermatol 1989;20:791-6.

Katz HI, Prawer SE, Medansky RS, et al. Intermittent corticosteroid maintenance treatment of psoriasis: a double-blind multicenter trial of augmented betamethasone dipropionate ointment in a pulse dose treatment regimen. Dermatologica 1991;183:269-74.

Katz HI, Prawer SE, Mooney JJ, et al. Preatrophy: covert sign of thinned skin. J Am Acad Dermatol 1989;20:731-5.

Kligman AM. Adverse effects of topical corticosteroids. In: Christophers E, Schopf E, Kligman AM, et al, editors. Topical corticosteroid therapy: a novel approach to safer drugs. New York: Raven Press, 1988:181-7.

Kligman AM, Frosch PJ. Steroid addiction. Int J Dermatol 1979;18:23-31.

Lepoittevin JP, Drieghe J, Dooms-Goossens A. Studies in patients with corticosteroid contact allergy: understanding cross-reactivity among different steroids. Arch Dermatol 1995;131:31-7.

Marks R. Survey of methods for assessment of corticosteroid atrophogenicity. In: Christophers E, Schopf E, Kligman AM, et al, editors. Topical corticosteroid therapy: a novel approach to safer drugs. New York: Raven Press, 1988:105-10.

McKenzie AW, Stoughton RB. Method for comparing percutaneous absorption of steroids. Arch Dermatol 1962;86:608-10.

five star hotel in ThiraQueille C, Pommarede R, Saurat J. Efficacy versus systemic effects of six topical steroids in the treatment of atopic dermatitis of childhood. Pediatr Dermatol 1984;1:246-53.

Schlagel CA, Sanborn EC. The weights of topical preparations required for total and partial body inunction. J Invest Dermatol 1964;42:253-6.

Shah VP, Peck CC, Skelly JP. `Vasoconstriction'-skin blanching-assay for glucocorticoids: a critique. Arch Dermatol 1989;125:1558-61.

Singh G, Singh PK. Tachyphylaxis to topical steroid measured by histamine-induced wheal suppression. Int J Dermatol 1986;25:324-6.

Stoughton RB. Are generic formulations equivalent to trade name topical glucocorticoids? Arch Dermatol 1987;123:1312-4.

Stoughton RB. The vasoconstrictor assay in bioequivalence testing: practical concerns and recent developments. Int J Dermatol 1992;31:26-8.

Timmins P, Gray EA. Degradation of hydrocortisone in a zinc oxide lotion.. J Clin Hosp Pharm 1983;8:79-85.

Turpeinen M, Salo OP, Leisti S. Effect of percutaneous absorption of hydrocortisone on adrenocortical responsiveness in infants with severe skin disease. Br J Dermatol 1986;115:475-84.

Vermeer BJ, Heremans GFP. A case of growth retardation and Cushing's syndrome due to excessive application of betamethasone-17-valerate ointment. Dermatologica 1974;149:299-304.

Yohn JJ, Weston WL. Topical glucocorticosteroids. Curr Probl Dermatol 1990;2:31-63.