A Review of Treatment of Mild to Moderate Pediatric Atopic Dermatitis

A specialist shares insights on the management of patients with atopic dermatitis with an emphasis on topical interventions and long-term management strategies.

By Adelaide A. Hebert, MD

Treatment of AD is aimed at managing symptoms with the ultimate goal of inducing remission and reducing the frequency and severity of flares.^1,2 As such, the approach to each patient must be individualized to the specific presentation and must be modified over the long-term to meet the patient’s needs.

Skin Care and Barrier Repair Devices

Proper skin care is essential for management of atopic dermatitis. Patients should bathe with mild, soap-free cleansers that are free of fragrances and detergents (bubble baths).³ Standard emollients can be applied to improve skin hydration and reduce dryness and flaking. Applying emollients immediately after bathing and patting the skin dry maximizes absorption and increases skin hydration.

New barrier repair devices have come to market. These are designed specifically to address the underlying defects in the epidermal barrier of patients with AD. Prescription barrier repair devices include MimyX (Stiefel/GlaxoSmithKline), Atopiclair (Graceway Pharmaceuticals), EpiCeram (Promius Pharma), and Hylatopic Plus (Onset Therapeutics), some of which contain ceramides, cholesterol, and fatty acids along with proprietary ingredients intended to increase hydration and reduce inflammation. Over-the-counter products formulated with ceramides and intended to support barrier function include CeraVe (Coria Laboratories), the Aveeno Eczema Care line of products (Johnson & Johnson Consumer Health), and Cetaphil Restoraderm (Galderma).

By replacing these key lipids, which are reduced in atopic dermatitis, these topical agents repair barrier function, reduce trans-epidermal water loss, and increase the moisture content of the skin. These non-steroidal emollients effectively relieve symptoms associated with AD, including pruritus, burning, and xerosis and can reduce the need for topical corticosteroid use.^4-6 Application of these agents is safe for all parts of the body including the face, without the adverse effects associated with the use of topical corticosteroids.

Atopiclair is reported to be effective as a monotherapy in treating mild-to-moderate atopic dermatitis in infants and children.^7,8 In a randomized trial of 113 subjects, EpiCeram was reported to be equally effective as fluticasone proprionate 0.05% for treating atopic dermatitis.

Topical corticosteroids

Topical corticosteroids, which have been the mainstay of atopic dermatitis therapy for more than 40 years, are still considered first-line therapy for acute flares.¹⁰ Most patients with atopic dermatitis will be managed with a topical corticosteroid at some point during the course of treatment. However, corticosteroids are not ideal for long-term management of AD. With immunosuppressive, anti-inflammatory, vasoconstrictive, and antiproliferative properties,¹¹ topical corticosteroids suppress the release of proinflammatory cytokines and reduce the activity of various immune cells, including T lymphocytes, monocytes, and macrophages.¹²

Despite their therapeutic utility, topical corticosteroids are associated with potential local and systemic adverse effects, the incidence of which increases with the potency of corticosteroid used and the duration of therapy. When applied to areas of thin skin, such as the face, groin, neck, and axillae, topical corticosteroids may have greater potency than when applied to other anatomic locations, and local adverse effects tend to occur more frequently in these areas.1 Potential local adverse effects of topical corticosteroid use include skin atrophy, striae, prominent telangiectasias, perioral dermatitis, acne, worsening of fungal infections, hypopigmentation, rosacea, cataracts, and glaucoma. When topical cortisosteroids are prescribed and used properly, complications associated with use rarely develop. However, potential systemic adverse effects such as reduction of the linear growth rate in children and reduced bone density have been reported with chronic use of topical steroid preparations.^13,14

Selection of a topical corticosteroid is based upon the potency (from low to super-potent) and vehicle type. Due to the fact that the risk of adverse events increases with the potency of the corticosteroid, the site of application, and the duration of use, the clinician must weigh these considerations when selecting an agent. A general approach is to treat an acute flare of atopic dermatitis with up to two to four weeks of medium-to-high-potency topical corticosteroid ointments applied to the affected areas of spongiotic dermatitis to induce partial remission. Once partial remission is attained, the clinician may taper down the frequency to as little as twice-weekly application of a less-potent preparation to maintain longterm control of disease activity.^1,3,15 When topical corticosteroids are used for maintenance therapy, the least potent, effective formulation should be selected.¹

Some parents and even clinicians eschew the use of higher potency corticosteroids citing concerns about side effect risks. However, using higher potency corticosteroids in appropriate settings may actually reduce the patient’s exposure to the corticosteroid, and thereby possibly reduce the risk of adverse events. A randomized, controlled trial in children with mild-to-moderate atopic dermatitis revealed that shorter periods of potent topical corticosteroid use are as effective as prolonged use of a low-potency preparation in controlling flares. Reducing the number of daily applications may be an appropriate method to decrease overall corticosteroid exposure. Interestingly, one large systematic review found that using twice-daily application of topical corticosteroid was no more effective than oncedaily application.¹⁰

Although uncommon, reversible suppression of the hypothalamic–pituitary–adrenal (HPA) axis can occur with frequent and chronic use of topical steroids. This systemic side effect seems to be associated with increased percutaneous absorption caused by a higher ratio of skin surface area to body mass in children. Systemic absorption occurs more often in children with severe disease, possibly due to the disrupted barrier and subsequently increased absorption of drug. Long-term topical corticosteroid use is generally not recommended. If this therapeutic approach is mandated by the patient’s overall status, care should progress under careful physician supervision and may require dietary intervention (such as adequate calcium and vitamin D intake) to help offset systemic side effects. Given the known risks associated with prolonged use of topical corticosteroids, controlled studies of extended durations of use are limited. However, data support the safety of specific formulations for continuous use beyond two weeks. Application of fluticasone proprionate cream and lotion 0.05% (Cutivate Cream and Lotion, PharmaDerm),^17,18 desonide hydrogel and foam 0.05% (Desonate hydrogel, Intendis;¹⁹ Verdeso foam, Stiefel/GlaxoSmithKline²⁰), and hydrocortisone butyrate 0.1% (Locoid Lipocream, Triax)²¹ for up to four weeks has been found to be safe in children as young as three months.

Wet wrap therapy in conjunction with topical corticosteroids (See p. 45 in this edition) is gaining popularity in AD management.

Topical calcineurin inhibitors

Now used for nearly a decade, topical calcineurin inhibitors (TCIs) tacrolimus and pimecrolimus are FDA-approved for use as second-line therapy in treating atopic dermatitis in immunocompetent patients over the age of two years. The product labeling indicates that these agents are to be used for short-term and non-continuous chronic treatment in children ages two years of age and older who have failed to respond to other topical pharmacological treatments.^22,23 Tacrolimus ointment 0.03% (approved for children ages two to 15 years) and 0.1% are approved to treat moderate-to-severe atopic dermatitis, whereas pimecrolimus cream 1% is approved to treat mild-to-moderate atopic dermatitis. Both tacrolimus and pimecrolimus decrease skin inflammation by inhibiting Tcell activation and the transcription and release of inflammatory cytokines.²⁴

Clinically, TCIs are thought of as steroid-sparing agents. As such, they are typically used for maintenance therapy as an alternative to topical corticosteroids and are advantageous in sensitive skin areas, such as the head and neck, that are more prone to adverse effects associated with the use of topical corticosteroids. 25 A common therapeutic approach is to initiate therapy with TCIs at the same time that a topical corticosteroid is introduced.

Multiple studies have shown that twice-daily application of topical pimecrolimus cream 1% for three to six weeks and even up to two years was well tolerated, effectively controlled atopic dermatitis disease activity, reduced the number and severity of flares, and reduced the need for topical corticosteroid treatment. ^26-28 Long-term studies of topical tacrolimus show rapid efficacy and safety for the management of atopic dermatitis in children and adults for up to four years. Results of a four-year long-term study showed that the adverse events profile was similar to that reported in previous one-year studies; no new adverse events were reported.^24,29-35

Reviews that compare topical tacrolimus to topical pimecrolimus found no significant difference in the overall safety or efficacy between tacrolimus ointment 0.03% and pimecrolimus cream 0.1%.³⁵ A review of three randomized, controlled trials comparing tacrolimus to pimecrolimus found that tacrolimus was more effective and had a more rapid onset of action than pimecrolimus in treating adults and children with moderate-to-severe atopic dermatitis.³⁴ There were no significant differences in the incidence of adverse events between the therapies.

Data and clinical experience suggest that topical tacrolimus application may be associated with a higher incidence of application site reactions—which include erythema, irritation, burning, and pruritus— and that these reactions persist for a longer amount of time.^24,28,35,36 When TCI therapy is implemented in conjunction with a topical corticosteroid, the latter may minimize the development of application site reactions.

Some concerns about lympho proliferative disease, immunosuppression, and nonmelanoma skin cancer associated with the use of topical application of tacrolimus and pimecrolimus have been raised. Studies show that there is some percutaneous absorption associated with topical application of these agents, however the amount is not significant to cause immunosuppression comparable to that experienced by immunodeficient patients or transplant patients who require systemic immunosuppressants to prevent organ rejection.^24,28 Topical pimecrolimus has been found to have less percutaneous absorption than both topical tacrolimus and topical corticosteroids, perhaps due to its lipophilicity and higher molecular weight.37 Initial studies of patients with exposure to topical calcineurin inhibitors show no association with an increased risk of nonmelanoma skin cancer.³⁸

Overcoming Challenges

Despite advancements in understanding the pathogenesis of AD, including genetic factors and the role of barrier dysfunction, treatment often remains challenging. Standard and emerging therapies can provide notable improvement in symptoms and improve outcomes. Key to success is devising a management strategy that meets the patient’s and caregivers’ needs while optimizing adherence. Studies confirm the importance of a well-developed patient–provider relationship, which is associated with clinical improvement of atopic dermatitis and decreased use of topical corticosteroids and calcineurin inhibitors.³⁹

One important area of dialogue is the relapsingremitting course of atopic dermatitis. Patients and families must recognize this reality in order to develop appropriate short- and long-term treatment expectations. Although spontaneous remission may occur, there is no “cure” for AD.

To enhance therapeutic outcomes, clinicians must educate patients/caregivers effectively about the proper use of topical corticosteroids, TCIs, and emollients.

Written instructions or written action plans (WAP) have been shown to improve adherence and treatment outcomes in patients with asthma and appear to provide benefit in the management of AD.⁴⁰ It seems likely that written action plans can reduce therapeutic errors (improper application, use of too little or too much medication, even pharmacy prescription filling errors) at home and may reduce the need for calls to the clinic. Proper education of caregivers and patients and good compliance with a regimen that control flares and allows maintenance strategies is essential to a favorable outcome.

Written instructions or written action plans (WAP) have been shown to improve adherence and treatment outcomes in patients with asthma and appear to provide benefit in the management of AD.40 It seems likely that written action plans can reduce therapeutic errors (improper application, use of too little or too much medication, even pharmacy prescription filling errors) at home and may reduce the need for calls to the clinic. Proper education of caregivers and patients and good compliance with a regimen that control flares and allows maintenance strategies is essential to a favorable outcome.

Eichenfield LF, Hanifin JM, Luger TA et al. Consensus conference on pediatric atopic dermatitis. J Am Acad Dermatol 2003;49:1088–95.
Hani?n JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Derm Venereol Suppl (Stockh) 1980;92:44–47.
Nicol NH. Use of moisturizers in dermatologic disease: the role of healthcare providers in optimizing treatment outcomes. Cutis 2005;76(6 Suppl):S26–31.
Madaan A. Epiceram for the treatment of atopic dermatitis. Drugs Today (Barc) 2008;44:751–5.
Veraldi S, De Micheli P, Schianchi R et al. Treatment of pruritus in mild-to-moderate atopic dermatitis with a topical non-steroidal agent. J Drugs Dermatol 2009;8:537–9.
Abramovits W, Perlmutter A. MimyX cream. Skinmed. 2006 Jan-Feb;5(1):29-30.
Patrizi A, Capitanio B, Neri I et al. A double-blind, randomized, vehicle-controlled clinical study to evaluate the efficacy and safety of MAS063DP (ATOPICLAIR) in the management of atopic dermatitis in paediatric patients. Pediatr Allergy Immunol 2008;19:619–25.
Boguniewicz M, Zeichner JA, Eichenfield LF et al. MAS063DP is effective monotherapy for mild to moderate atopic dermatitis in infants and children: a multicenter, randomized, vehicle-controlled study. J Pediatr 2008;152:854–9.
Sugarman J, Parish LJ. IID 2008. Kyoto; Japan: 2008. A topical lipid-based barrier repair formulation (EpiCeram cream) is highly-effective monotherapy for moderate-to-severe pediatric atopic dermatitis.
Hoare C, Li Wan Po A, Williams H. Systematic review of treatment for atopic dermatitis. Health Technol Assess 200;4:1–191.
Charman C, William H. The use of corticosteroids and costicosteroid phobia in atopic dermatitis. Clin Dermatol 2003;21:193–200.
Norris DA. Mechanisms of action of topical therapies and the rationale for combination therapy. J Am Acad Dermatol 2005;53(1 suppl):S17-S25.
Drake LA, Dinehart SM, Farmer ER, et al. Guidelines of care for the use of topical glucocorticosteroids. American Academy of Dermatology. J Am Acad Dermatol 1996;35:615-9.
Haeck IM, Hamdy NA, Timmer-de Mik L, et al. Low bone density in adult patients with moderate to severe atopic dermatitis. Br J Dermatol 2009;161:1248-54
Hanifin JM, Gupta AK, Rajagopalan R. Intermittent dosing of fluticasone proprionate cream for reducing the risk of relapse in atopic dermatitis patients. Br J Dermatol 2002;147:528-537.
Thomas KS, Armstrong S, Avery A et al. Randomized controlled trial of short bursts of a potent topical corticosteroid versus prolonged use of a mild preparation for children with mild to moderate atopic dermatitis. BMJ 2002;324:768.
Friedlander SF, Hebert AA, Allen DB. Safety of fluticasone proprionate cream 0.05% for the treatment of severe and extensive atopic dermatitis in children as young as 3 months. J Am Acad Dermatol 2002;46:387–93.
Hebert AA, Friedlander SF, Allen DB. Topical fluticasone proprionate lotion does not cause HPA axis suppression. J Pediatr 2006;149:378–82.
Hebert AA, Cook-Bolden FE, Basu S, Calvarese B, Trancik RJ; Desonide Hydrogel Study Group. Safety and efficacy of desonide hydrogel 0.05% in pediatric subjects with atopic dermatitis. J Drugs Dermatol. 2007 Feb;6(2):175-81.
Hebert AA; Desonide Foam Phase III Clinical Study Group. Desonide foam 0.05%: Safety in children as young as 3 months. J Am Acad Dermatol. 2008 Aug;59(2):334-40.
Abramovits W, Oquendo M. Hydrocortisone butyrate 0.1% lipocream in pediatric patients with atopic dermatitis. Skinmed. 2010 Mar-Apr;8(2):72-9
Protopic [prescribing information]. Deerfield, IL: Astellas Pharma US, Inc; 2006
Elidel [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals; 2006.
Hultsch T, Kapp A, Stergel J. Immunomodulation and safety of topical calcineurin inhibitors for the treament of atopic dermatitis. Dermatology 2005;211:174–87.
Chapman MS, Schachner LA, Breneman D et al. Tacrolimus ointment 0.03% shows ef?cacy and safety in pediatric and adult patients with mild to moderate atopic dermatitis. J Am Acad Dermatol 2005;53:S177–85.
Wahn U, Goodfield M et al. Efficacy and safety of pimecrolimus cream in the long-term management of atopic dermatitis in children. Pediatrics 2002;110(1).
Papp KA, Werfel T Folster-Holst R et al. Long-term control of atopic dermatitis with pimecrolimus cream 1% in infants and young children: a two-year study. J Am Acad Dermatol 2005;52:240–6.
Iskedijan M, Piwko C, Shear N et al. Topical calcineurin inhibitors in the treatment of atopic dermatitis: a meta-analysis of current evidence. J Am Acad Dermatol 2004;5:267–79.
Kang S, Lucky AW, Pariser D, et al. Long-term safety and efficacy of tacrolimus ointment for the treatment of atopic dermatitis in children. J Am Acad Dermatol 2001;44(1 Suppl.):S58–64.
Hanifin JM, Paller A, Eichenfield L et al. Long term (up to 4 years) efficacy and safety of tacrolimus ointments in patients with atopic dermatitis. J Am Acad Dermatol 2005;(2 suppl):S186-S194.
Beck L. The efficacy and safety of tacrolimus ointment: a clinical review. J Am Acad Dermatol 2005;53:S165–70.
Koo JY, Fleischer AB, Abramovits W et al. Tacrolimus ointment is safe and effective in the treatment of atopic dermatitis: results in 8000 patients. J Am Acad Dermatol 2005;53:S195-S205.
Chapman MS, Schachner LA, Breneman D et al. Tacrolimus ointment 0.03% shows ef?cacy and safety in pediatric and adult patients with mild to moderate atopic dermatitis. J Am Acad Dermatol 2005;53:S177–85.
Paller A, Lebwohl M, Fleischer AB et al. Tacrolimus ointment is more effective than pimecrolimus cream with a similar safety pro?le in the treatment of atopic dermatitis: Results from 3 randomized, comparative studies J Am Acad Dermatol 2005;52:810–22.
Kempers S, Boguniewicz M, Carter E et al. A randomized investigator-blinded study comparing pimecrolimus cream 1% with tacrolimus ointment 0.03% in the treatment of pediatric patients with moderate atopic dermatitis. J Am Acad Dermatol 2004;51:515–25.
Breuer K, Werfel T, Kapp A. Safety and efficacy of topical calcineurin inhibitors in the treatment of childhood atopic dermatitis. Am J Clin Dermatol 2005;6:65–77.
Billich A, Aschauer H, Aszodi A et al: Percutaneous absorption of drugs used in atopic eczema: pimecrolimus permeates less through skin than corticosteroids and tacrolimus. Int J Pharm 2004;269:29–35.
Margolis D, Hoffstad O, Bilker W. Lack of association between exposure to topical calcineurin inhibitors and skin cancer in adults. Dermatology 2007;214:289–95.
Boguniewicz M, Sampson H, Leung SB et al. Effects of cefuroxime axetil on Staphylococcus aureus colonization and superantigen production in atopic dermatitis. J Allergy Clin Immunol 2001;108:651–2.
Chisolm, S. S., Taylor, S. L., Balkrishnan, R., Feldman, S. R., Chisolm, Sarah S., Taylor, Sarah L. Written action plans: potential for improving outcomes in children with atopic dermatitis. Journal of the American Academy of Dermatology 2008; 59: 677-683.

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