Update on Topical Management of Mild to Moderate Pediatric Atopic Dermatitis
Knowledge of epidermal barrier function and the role that dysfunction plays in diseases such as atopic dermatitis has certainly increased in recent years. This knowledge on the molecular level has improved our general understanding of these diseases and influenced the approach to treatment through the introduction of a whole new class of barrier repair therapies. In some sense, the emergence of barrier repair therapies has overshadowed well-established treatment options for mild to moderate atopic dermatitis that deserve thoughtful consideration by clinicians. The reality is that most patients require a combination approach to treatment that incorporates both conventional topical therapies and barrier repair. Ahead, I will review the approach to topical treatment of mild to moderate atopic dermatitis (AD) with an emphasis on the safe and effective use of corticosteroids and topical calcineurin inhibitors along with newer interventions.
Atopic Dermatitis Basics
Dermatology clinicians are familiar with the classic symptoms of mild to moderate atopic dermatitis, which may vary based on patient age. If there are clinical challenges, they often relate to treatment. Management of many cases of mild to moderate AD would seem, at first evaluation, to be relatively straightforward. However, when issues such as non-adherence, patient confusion about drug safety, and frustration with previous therapy enter the equation, apparently simple cases can become complex. Key to counteracting these confounders is to communicate with and effectively educate the patient.
Dialogue begins with assessment of the patient’s treatment history. Next comes discussion of skin care basics, considered a cornerstone of AD management.1 Every atopic dermatitis patient requires education on basic skin care and moisturization. This includes, but is not limited to, proper selection of cleansers and bathing practices, selection and application of moisturizers, and use of clothes detergents and laundering. During this initial discussion, it may also be helpful to ask questions about any vehicle preferences (cream versus ointment, for example) that the patient or parent may have.
Soap-free, gentle, moisturizing, liquid skin cleansers are preferred for bathing, while bar soaps are to be avoided. Patients/parents can select the general use moisturizer they prefer, so long as it is fragrance- and dye-free. Generally, the fewer ingredients a formulation contains the less likely it is to cause irritation or allergy. The moisturizer will be used by the patient anytime that the skin feels dry, tight, or even itchy, as rubbing moisturizer into the skin is non-traumatic—unlike scratching.
The impact of laundry detergent on atopic skin is controversial. Any patient with a history of exacerbation linked to laundry detergent or who is concerned about possible exacerbation can be advised to use a fragrance- and dye-free fabric wash, consider a second rinse cycle, and avoid fabric softeners. Given that fragrance- and dye-free options are readily available at a similar cost to standard detergents, there is no harm in patients using them.
Topical corticosteroids and topical calcineurin inhibitors (TCIs) remain the most widely used pharmacologic interventions for mild to moderate atopic dermatitis.1,2,3 Corticosteroids are primarily anti-inflammatory, regulating mediator release and function, inflammatory cell function, and release of lysosomal enzymes.4,5 Though they are safe and effective when administered properly,2 topical corticosteroids are associated with well-known adverse effects, including atrophy, striae, acneiform eruption, purpura, hypertrichosis, pigmentation alterations, delayed wound healing, and exacerbation of skin infections.6 Contact sensitization against corticosteroids is possible but still relatively uncommon.6
To reduce the risk of adverse events, corticosteroid use should be limited to brief durations. The recommended frequency of application and duration of therapy will depend on the specific presentation and the prescriber’s preference. It should be noted that once-daily application of topical corticosteroids has been shown to confer benefits similar to more frequent application, suggesting that the more convenient once-a-day approach is worth advocating.3 In terms of therapeutic duration, some clinicians prefer a step-wise approach to corticosteroid therapy, initiating therapy with a high potency corticosteroid for several days before introducing a lower-potency steroid for a follow-up interval. Others prefer a “burst” approach in which the patient uses a higherpotency steroid for a specific interval (usually two weeks) followed by an interval of no treatment or drug holiday. There is no compelling evidence that favors one method over the other.1 A practical consideration for the potency tapering approach is that it requires dual prescriptions and thus dual co-pays for the patient.
Technically, TCIs (pimecrolimus, Elidel (Coria) and tacrolimus, Protopic (Astellas)) are approved as second-line treatments for AD,1 and they were initially embraced by the dermatology community as “steroid-sparing” agents. However, their actual use in the management of atopic dermatitis is variable. TCIs are immunomodulatory, reducing inflammation by inhibiting calcineurin and its effects on Th2 T cells. They are approved for noncontinuous use and are not intended for use in individuals under the age of two. A black box warning added to these agents notes that the long-term safety of their use has not been established and suggests that there is a potential cancer risk associated with their use. This warning on the topical TCIs was based on evidence for systemic exposure to TCIs, including those used in transplant patients.7
Many clinicians favor TCIs, which have no risk for atrophy,3 for use on “thin skin” such as on the face or in the leg creases.8 Patients may prefer the feel of pimecrolimus cream over tacrolimus ointment formulation for these anatomic sites. Rather than as an alternative to corticosteroids for flared AD, TCIs are often used as a maintenance therapy once corticosteroids have brought the flare under control. TCIs may be initiated along with topical corticosteroid therapy and continued once the corticosteroid has been withdrawn. If TCIs are used very early in the genesis of an AD flare, they may be able to prevent exacerbation of eczema.
Given the current warning, many clinicians prefer that patients not use TCIs on a continuous basis. In some cases, intermittent use one to three times per week is recommended. In other cases, clinicians advise therapeutic holidays for well-controlled atopic dermatitis, instructing patients to reinstate the TCI and/or topical corticosteroid at the very first sign of a possible flare. An analysis of the available data on the TCIs shows that they are safe and effective for continuous short-term use and for intermittent use for up to four years.9
Drug Safety and Patient Education
The public is generally aware of the potential adverse effects associated with topical corticosteroid use. However, they may not understand the nature of the risk, including the influence of corticosteroid potency and therapeutic duration. Patients concerned about corticosteroid safety may not apply the drugs properly or may forgo application altogether.10 Consider a recent study showing that up to 87 percent of patients are fearful of topical corticosteroid use. More than one-third (36 percent) of patients said that fears of topical corticosteroids have led them to be non-adherent. Topical corticosteroid phobia did not correlate with atopic dermatitis severity. However, phobia did correlate with need for reassurance, the belief that topical corticosteroids pass through the skin into the bloodstream, a prior adverse event, inconsistent information about the quantity of cream to apply, a desire to self-treat for the shortest time possible, and poor treatment adherence.10
There is also evidence that the black box warnings on TCIs have led to changes in patient care.7 In a recently published survey of dermatologists, about two-thirds of respondents indicated that between 20 and 50 percent of their patients are not adequately controlled for long-term AD maintenance since the addition of the black box. Responses indicated that some patients are now being treated with potentially more dangerous systemic therapies, including corticosteroids, and phototherapy.
Clearly patient education about treatment selection and use is essential. Clinicians should directly address therapeutic safety with patients. While a healthy respect for topical corticosteroids is desirable, patients need not fear these agents when used under physician orders. Similarly, patients should be assured that the prescriber is aware of the boxed warning on TCIs but that he or she believes the risk to be minimal, is prescribing the TCI in a manner considered safe according to the standard of care, and believes treatment will provide benefits for the patient.
Building in Barrier Therapies
There is ample support for the use of barrier repair therapies within the atopic dermatitis treatment regimen. Atopic dermatitis is now recognized as a disease of epidermal barrier dysfunction. Research links abnormalities in the epidermal barrier to the pathogenesis of atopic dermatitis specifically and to cutaneous inflammation generally.11,12 Barrier repair therapies are designed to replace ceramides and/or fatty acids in the epidermis in order to restore the integrity of the barrier and reduce inflammation. Barrier repair therapies have been suggested as potential adjuncts to conventional topical therapies because they offer a different therapeutic target than conventional topical agents.13 Further evidence to support the use of barrier repair therapies in conjunction with conventional therapeutics derives from recent suggestions that these agents can help to reduce undesirable effects of topical drugs on the epidermal barrier.14
A Multi-Modal Approach
No cure for atopic dermatitis exists, but available therapies offer a reasonable chance of controlling the disease, especially among individuals with mild to moderate disease. Education and communication and proper basic skin care are essential for all patients. For acute flares, topical corticosteroids and/or TCIs are indicated. Barrier repair therapies are appropriate for many patients to support clearance. For maintenance of clearance, TCIs and/or barrier repair therapies are reliable. Patients and their parents should be instructed on “rescue” strategies to be implemented at the first sign of an AD flare.
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