Continuing Education Activity

Topical corticosteroids play a major role in the treatment of many dermatologic conditions. They are FDA-approved and indicated for the use of inflammatory and pruritic presentations of dermatologic conditions. The well-known indications are for diseases such as psoriasis, limited areas of vitiligo, eczema, atopic dermatitis, phimosis, acute radiation dermatitis, lichen planus, lichen simplex chronicus, discoid lupus erythematosus, and lichen sclerosis. They are effective for conditions involving hyper-proliferation, immunological, and inflammatory properties. This activity outlines the indications, mechanism of action, methods of administration, important adverse effects, contraindications, toxicity, and monitoring, of topical corticosteroids so providers can direct patient therapy where they are indicated as part of the interprofessional team.

Objectives:

• Identify the three predominant mechanisms of action of topical corticosteroids.
• Review the indications for using topical corticosteroids.
• Summarize the adverse event profile of topical corticosteroids, as well as contraindications to their use.
• Explain the importance of improving care coordination among the interprofessional team to enhance the delivery of care for patients who can benefit from therapy with topical corticosteroids.

Indications

Topical corticosteroids play a major role in the treatment of many dermatologic conditions. They are FDA-approved and indicated for the use of inflammatory and pruritic presentations of dermatologic conditions. The well-known indications are for diseases such as psoriasis, limited areas of vitiligo, eczema, atopic dermatitis, phimosis, acute radiation dermatitis, lichen planus, lichen simplex chronicus, discoid lupus erythematosus, and lichen sclerosis.[1] They are effective for conditions involving hyper-proliferation, immunological, and inflammatory properties.[2]

Mechanism of Action

The mechanism of action of topical corticosteroids is vast, consisting of anti-inflammatory, anti-mitotic, and immunosuppressive effects.[3]

The anti-inflammatory effect of topical corticosteroids consists of vasoconstriction, inhibition of the release of phospholipase A2, and a direct inhibitory effect on DNA and inflammatory transcription factors.[3][4]Vasoconstriction of the blood vessels within the upper dermis decreases the number of inflammatory mediators being delivered to the region applied.[3] The anti-inflammatory effect also occurs from the synthesis of lipocortin which inhibits phospholipase A2, ultimately decreasing the production of prostaglandins and leukotrienes.[4] Topical corticosteroids also act directly at the DNA level to increase the expression of anti-inflammatory genes and indirectly inhibit inflammatory transcription factors, such as NFkb, to decrease the expression of pro-inflammatory genes.[3]

The anti-mitotic effect of topical corticosteroids play a great role in the treatment of psoriasis; it is proposed that this decrease in epidermal mitosis is secondary to an increase in lipocortin, an endogenous glucocorticoid-regulated protein. An anti-mitotic effect is also present in the dermis which inhibits cell proliferation and collagen synthesis.[5][6]

The immunosuppressive effects of topical corticosteroids involve the inhibition of humoral factors involved in the inflammatory response as well as suppression of the maturation, differentiation, and proliferation of all immune cells.[5]

Administration

Topical corticosteroids are administered topically; however, successful administration depends upon obtaining an accurate diagnosis, choosing the correct drug, selecting the appropriate vehicle and potency, and the frequency of application.[1]

The vehicle is the carrier of the drug. The vehicle selection depends on the region affected and the type of lesion present. It also functions to hydrate the skin and increase absorption. The vehicle options include the following[7]: 

• Ointments - administered for thick hyper-keratotic lesions; the most potent vehicle since they are the most occlusive and should not be administered on hair-bearing regions because it may result in folliculitis[1]
• Creams - less potent than ointment but cosmetically more appealing since they leave no residue; the drying, non-occlusive nature leads to their administration for acute exudative inflammation and dermatitis within the intertriginous areas.[1]
• Lotions - less occlusive and greasy; work well in hair-bearing regions
• Gels - like lotions, less occlusive and greasy; work well in hair-bearing regions; more beneficial for the scalp as they do not cause matting of thleast occlusive and greasye hair
• Foams - highly effective for steroid delivery to the scalp but are costly[8] 

The potency of topical corticosteroids is the amount of drug needed to produce a desired therapeutic effect. The gold standard for determining potency is the vasoconstrictor assay which measures the vasoconstrictive properties based upon cutaneous vasoconstriction.[9] The United States classification consists of seven classes, with class I superpotent and class VII least potent.[10]

Class I superpotent corticosteroids include clobetasol propionate 0.05% in any vehicle, augmented betamethasone dipropionate 0.05% gel or ointment, diflorasone diacetate 0.05% ointment, fluocinonide 0.1% cream, and halobetasol propionate 0.05% cream or ointment.[1]   

Class II high-potency corticosteroids include amcinonide 0.1% ointment, augmented betamethasone dipropionate 0.05% cream or lotion, betamethasone dipropionate 0.05% ointment, desoximetasone cream or gel or ointment, diflorasone diacetate 0.05% cream, fluocinonide 0.05% cream or gel or ointment, and halcinonide 0.1% cream or ointment or solution.[1]

Class III medium- to high-potency corticosteroids include amcinonide 0.1% cream, betamethasone dipropionate 0.05% cream, fluticasone propionate 0.005% ointment, and triamcinolone acetonide 0.5% cream or ointment.[1]

Class IV and V medium-potency corticosteroids include betamethasone valerate 0.1% cream or lotion or foam, desoximetasone 0.05% cream, Fluocinolone acetonide 0.025% cream or ointment, fluticasone propionate 0.05% cream, hydrocortisone butyrate 0.1% ointment, hydrocortisone probutate 0.1% cream, hydrocortisone valerate 0.2% cream or ointment,   mometasone furoate 0.1% cream or lotion or ointment, triamcinolone acetonide 0.025% cream or lotion or ointment, and triamcinolone acetonide 0.1% cream or lotion or ointment.[1]

Class VI low-potency corticosteroids include alclometasone dipropionate 0.05% cream or ointment, desonide 0.05% in any vehicle, fluocinolone 0.01% cream, and hydrocortisone butyrate 0.1% cream.[1]

Class VII least-potent corticosteroids include hydrocortisone 1% and 2.5% cream or lotion or ointment.[1]

Corticosteroids are better absorbed and more permeable in regions of thin epidermis, such as the eyelid, compared to thicker regions of epidermis, such as the sole. The penetration difference between the two varies by 300 fold.[11]The penetration increases two- to ten-fold in diseased states, such as inflammation and desquamation.[1][12] High-potency steroids are used for the palms and soles, due to the thick stratum corneum, and in nonfacial/nonintertriginous areas for severe dermatoses, such as psoriasis and severe atopic and contact dermatitis. [1] Medium- to high-potency steroids are useful for regions of thin epidermis and areas of occlusion, such as the eyelid and axilla, respectively.[8] Low-to-medium strength preparations should be used for large surface areas to decrease the risk of systemic absorption. 1917[1]

The amount of steroid used plays a great part in the efficacy of treatment but also in avoiding adverse effects from overuse. One fingertip unit (FTU) is equal to 0.5 grams. The suggested dose of FTU is dependent upon the body region being treated. Topical corticosteroids are recommended for once to twice daily use.[13] A study regarding topical corticosteroid use for atopic dermatitis demonstrated that there was no beneficial evidence to applying topical corticosteroid more than once per day. Applying it more often only resulted in an increase in adverse effects.[14]

Adverse Effects

The adverse effects of topical corticosteroids can be divided into local and systemic effects. Local adverse effects occur with prolonged treatment and are based on the topical steroid potency, vehicle, and application site. The most common local effects include atrophy, striae, rosacea, perioral dermatitis, acne, and purpura.[6]

Skin atrophy is the most common adverse effect and occurs due to the anti-mitotic effect of topical corticosteroids.[6] Topical steroid causes the skin to undergo 3 phases: preatrophy, atrophy, and tachyphylaxis. Atrophy occurs when there is a persistent use in the same region. This leads to epidermal thinning and increased resorption within the dermis ground substance. The loss of connective tissue leads to erythema, teleangiectasias, and purpura. Atrophy presents as a burning sensation; the vasoconstrictive effect of the topical corticosteroid relieves the burn.[4] Areas most at risk for atrophy are intertriginous due to thinner skin and increased occlusion. Atrophy is reversible with cessation of steroid use; however, it may take months for the skin to appear normal again.[6]

Tachyphylaxis is the result of the skin developing tolerance to the topical corticosteroid, which ultimately is a loss of vasoconstriction at the level of the capillaries. It has been demonstrated that the capillaries regain the ability to vasoconstrict after 4 days. For this reason, pulse therapy is recommended and the topical corticosteroid should be discontinued for 4 days if it has lost its effectiveness.[13]

Striae develop due to injury to the dermis and mechanical stress. Inflammation and edema of the dermis results in collagen deposition in the region of the mechanical stress. Striae appear histologically as scars and are permanent.[6]

Topical corticosteroid usage can result in acne formation due to the degradation of the follicular epithelium and an increase in the concentration of free fatty acids on the skin surface. This fosters an environment for bacteria growth, ultimately leading to comedogenesis.[6]

Steroid rosacea can occur when steroids are prescribed initially for erythema with or without pustules. If a low-dose potency topical corticosteroid is prescribed, it can lead to good results until the lesions reappear and higher potency steroid use is continuously needed.[6]

Perioral dermatitis occurs due to prolonged use of potent corticosteroids on the face. It presents as follicular pustules and papules on an erythematous base surround the perioral region but sparing the vermillion border.[6]

Less common local adverse effects include hypertrichosis, pigment alteration, and delayed wound healing. Systemic adverse effects are less likely to occur due to low percutaneous absorption; however, they can develop with the prolonged use of high-potency steroids on thin epidermal regions. The systemic adverse effects include glaucoma, hypothalamic-pituitary axis suppression, Cushing syndrome, hypertension, and hyperglycemia.[6]

Contraindications

Topical corticosteroids are contraindicated for bacterial infections as their anti-inflammatory and vasoconstrictive effect will mask the infection, ultimately delaying diagnosis and treatment. Topical steroids should also be avoided in impetigo, furuncles and carbuncles, cellulitis, erysipelas, lymphangitis, and erythrasma. Relative contraindications include candida and dermatophytes.[15] The immunosuppressive effects may result in persistent fungal infections that can be identified as tinea incognito, significant for increased spread and inflammation with pustule formation.[8]

Monitoring

Patients need to be monitored carefully as unsupervised use of these medications can result in local and systemic adverse effects. The duration of treatment should not be greater than 2 to 4 weeks, regardless of potency. High-potency steroids should not be administered for a longer than 2 weeks, and after this period, should be tapered to avoid adverse effects.[1][13] Guidelines to prevent adverse effects include the use of lower-potency steroids, morning-only applications, alternate-day treatment, and decreasing the extent of occlusion.[16]

Enhancing Healthcare Team Outcomes

Topical corticosteroids are one of the most commonly prescribed drugs in dermatology due to the rapid effect of relieving unwanted signs and symptoms. However, if they not properly prescribed or patients are not given adequate instructions, topical corticosteroid abuse can occur, resulting in adverse effects.[17] Ideally, dermatologists, nurses, general practitioners, and pharmacists should work together to enforce the way topical corticosteroids are applied. Realistically, expert advice is quickly forgotten, and the product label is the only direction that remains. A label stating “apply thinly or use sparingly” promotes anxiety that the product may be dangerous, resulting in poor adherence and treatment. To resolve this matter, the fingertip unit (FTU) was designed to make it easier for practitioners to explain to patients how much medication should be applied to different regions of the body. Taking the time to explain the FTU system can help patients feel confident that they are using an adequate amount of steroids. It has also been recommended that labels state to "apply enough to cover the affected area" and include an image of the fingertip unit and a chart demonstrating how many fingertip units should be applied to each body region so patients will receive appropriate treatment. Patients should also be advised not to exceed the prescribed treatment and to only discontinue use under medical supervision. Pharmacists are the last line of healthcare that the patient sees before using the medication and play an important role in enforcing the correct usage and ensuring patient understanding of the interprofessional team's treatment plan.[18]

Review Questions

• Access free multiple choice questions on this topic.
• Comment on this article.

References

1.

Ference JD, Last AR. Choosing topical corticosteroids. Am Fam Physician. 2009 Jan 15;79(2):135-40. [PubMed: 19178066]

2.

Giannotti B. Current treatment guidelines for topical corticosteroids. Drugs. 1988;36 Suppl 5:9-14. [PubMed: 3076133]

3.

Ahluwalia A. Topical glucocorticoids and the skin--mechanisms of action: an update. Mediators Inflamm. 1998;7(3):183-93. [PMC free article: PMC1781846] [PubMed: 9705606]

4.

Abraham A, Roga G. Topical steroid-damaged skin. Indian J Dermatol. 2014 Sep;59(5):456-9. [PMC free article: PMC4171912] [PubMed: 25284849]

5.

Uva L, Miguel D, Pinheiro C, Antunes J, Cruz D, Ferreira J, Filipe P. Mechanisms of action of topical corticosteroids in psoriasis. Int J Endocrinol. 2012;2012:561018. [PMC free article: PMC3508578] [PubMed: 23213332]

6.

Coondoo A, Phiske M, Verma S, Lahiri K. Side-effects of topical steroids: A long overdue revisit. Indian Dermatol Online J. 2014 Oct;5(4):416-25. [PMC free article: PMC4228634] [PubMed: 25396122]

7.

Lee NP, Arriola ER. Topical corticosteroids: back to basics. West J Med. 1999 Nov-Dec;171(5-6):351-3. [PMC free article: PMC1308757] [PubMed: 10639873]

8.

Rathi SK, D'Souza P. Rational and ethical use of topical corticosteroids based on safety and efficacy. Indian J Dermatol. 2012 Jul;57(4):251-9. [PMC free article: PMC3401837] [PubMed: 22837556]

9.

Goa KL. Clinical pharmacology and pharmacokinetic properties of topically applied corticosteroids. A review. Drugs. 1988;36 Suppl 5:51-61. [PubMed: 3076132]

10.

Jacob SE, Steele T. Corticosteroid classes: a quick reference guide including patch test substances and cross-reactivity. J Am Acad Dermatol. 2006 Apr;54(4):723-7. [PubMed: 16546601]

11.

Feldmann RJ, Maibach HI. Regional variation in percutaneous penetration of 14C cortisol in man. J Invest Dermatol. 1967 Feb;48(2):181-3. [PubMed: 6020682]

12.

Tadicherla S, Ross K, Shenefelt PD, Fenske NA. Topical corticosteroids in dermatology. J Drugs Dermatol. 2009 Dec;8(12):1093-105. [PubMed: 20027937]

13.

Drake LA, Dinehart SM, Farmer ER, Goltz RW, Graham GF, Hordinsky MK, Lewis CW, Pariser DM, Webster SB, Whitaker DC, Butler B, Lowery BJ, Raimer SA, Krafchik BR, Olsen E, Weston WL. Guidelines of care for the use of topical glucocorticosteroids. American Academy of Dermatology. J Am Acad Dermatol. 1996 Oct;35(4):615-9. [PubMed: 8859293]

14.

Williams HC. Established corticosteroid creams should be applied only once daily in patients with atopic eczema. BMJ. 2007 Jun 16;334(7606):1272. [PMC free article: PMC1892503] [PubMed: 17569936]

15.

Cornell RC. Contraindications for using topical steroids. West J Med. 1987 Oct;147(4):459-60. [PMC free article: PMC1025914] [PubMed: 18750337]

16.

Hengge UR, Ruzicka T, Schwartz RA, Cork MJ. Adverse effects of topical glucocorticosteroids. J Am Acad Dermatol. 2006 Jan;54(1):1-15; quiz 16-8. [PubMed: 16384751]

17.

Saraswat A. Ethical use of topical corticosteroids. Indian J Dermatol. 2014 Sep;59(5):469-72. [PMC free article: PMC4171915] [PubMed: 25284852]

18.

Bewley A., Dermatology Working Group. Expert consensus: time for a change in the way we advise our patients to use topical corticosteroids. Br J Dermatol. 2008 May;158(5):917-20. [PubMed: 18294314]

Disclosure: Sarah Gabros declares no relevant financial relationships with ineligible companies.

Disclosure: Trevor Nessel declares no relevant financial relationships with ineligible companies.

Disclosure: Patrick Zito declares no relevant financial relationships with ineligible companies.