A Comprehensive Management Guide for Atopic Dermatitis

Jennifer D. Peterson, MD; Lawrence S. Chan, MD

Disclosures

Dermatology Nursing. 2006;18(6):531-542. 

In This Article

Topical Therapy

Therapy for atopic dermatitis is multi-faceted and encompasses restoring the skin barrier function, using anti-inflammatory medications (topical or systemic), identifying and eliminating triggers, and secondary prevention. The skin barrier in AD is faulty with a decrease in the amount of and an abnormal ratio between skin lipids (most notably ceramide), which leads to increased transepidermal water loss (Chamlin et al., 2001; Darsow et al., 2005). Genetic mutations of the epidermal barrier protein filaggrin are a predisposing factor for AD (Palmer et al., 2006; Weidinger et al., 2006). Emollients are regarded as a standard of care in preventing and treating AD. When used as a moisturizing regimen in conjunction with steroids, emollients enhance the anti-inflammatory affect of topical steroids resulting in a steroid-sparing phenomenon (Hanifin et al., 2004; Hanifin et al., 1998). It is recommended that emollients be applied at least twice daily and immediately after bathing (Darsow et al., 2005).

Since their development over 50 years ago, topical corticosteroids have served as the first line of therapy for AD and this recommendation remains in the most up-to-date position of the European Academy of Dermatology and Venereology (Darsow et al., 2005). Topical steroids are anti-inflammatory medications and are classified according to their vasoconstrictor assays, with the most potent topical steroids in Class 1 and the least potent in Class 7 (see Table 4 ). Longer duration of therapy and more potent topical steroids have a higher potential for adverse effects. The amount of absorption of a topical steroid is influenced by the surface area of the skin, thickness of the skin (epidermis), the type of vehicle, drug concentration, and the presence of absence of occlusive dressings. Class 1 to 5 topical steroids should be avoided in areas of thinner skin, including the eyelids, face, mucous membranes, genitalia, and intertriginous areas, as these areas have increased likelihood of transepidermal corticosteroid absorption (Leung et al., 2004). In contrast, potent topical steroids may be needed on the palms and soles as the epidermis in these areas is much thicker (Brazzini & Pimpinelli, 2002). Children have a low body volume to skin surface area ratio, which allows for a greater absorption of corticosteroids leading to a higher potential for adverse affects. As a result, higher-potency steroids should be avoided in children (Paller et al., 2005). Local adverse effects of topical steroids include striae, skin atrophy, telangiectasias, perioral dermatitis, erythema, acne, glaucoma, and cataracts. Potential systemic adverse effects include growth suppression, suppression of the hypothalamic-pituitary-adrenal axis, and osteoporosis, and are most likely to occur with the use of high-potency steroids (Brazzini & Pimpinelli, 2002; Paller et al., 2005).

Benefits of topical steroids include a low-cost, wide variety of preparations, and proven clinical effectiveness (Leung et al., 2004). Topical steroids are available in a wide variety of vehicles including creams, lotions, ointments, solutions, gels, and foams. In general, ointments are more potent than creams because of superior ability to hydrate the stratum corneum (the top layer of the epidermis) which enhances absorption (Brazzini & Pimpinelli, 2002; Leung et al., 2004). Selection of a vehicle can also be based on the body area to which the medications will be applied. For example, ointments on hairy areas of the body can be messy, so foams and lotions are preferred. Sometimes in severe disease, occlusive dressings may be employed. Occlusive dressings have the advantage of increasing the penetration of a steroid and making therapy more effective, but they also increase the risk of side effects; therefore, they should not be used for prolonged periods of time (Brazzini & Pimpinelli, 2002).

The choice of a topical steroid should be tailored to each patient based on the potency, vehicle, lesion location, patient age, season, environment, socioeconomic class, prior medication(s), the presence or absence of infection, and patient preferences. Currently, it is recommended that the least-potent topical steroid be used (along with a good skin care regimen) to achieve the maximum benefit; then tapered, discontinued, or changed to less-potent topical steroid (Paller et al., 2005). Optimally, topical steroids should be used for only a few weeks in a continuous fashion and then used intermittently (for example, twice a week) (Hanifin et al., 2004; Paller et al., 2005). It is preferable for low-potency steroids to be used in maintenance therapy and mid to high-potency steroids to be used to treat flares (Leung et al., 2004). Pruritus can serve as a marker in evaluating a treatment response, and tapering of the steroid should not be attempted until pruritus has disappeared. Tapering of the topical steroid should be done gradually to avoid a flare (Darsow et al., 2005). Multiple large reviews have shown that once-a-day application of an appropriately selected topical steroid is as effective as twice-daily application (Green, Colquitt, Kirby, & Davidson, 2005; Hanifin et al., 2004). In children with mild-to-moderate AD, the use of intermittent, short cycles of potent steroids is safe and equivalent in effectiveness to the long-term use of weaker topical steroids (Hanifin et al., 2004).

In recent years, topical calcineurin inhibitors have become available for treating atopic dermatitis. These medications also have anti-inflammatory affects, but do not contain steroids. The two medications offered are pimecrolimus and tacrolimus, and both are approved to treat patients over age 2 (Darsow et al., 2005). Both medications decrease the extent, severity, and symptoms of AD (Hanifin et al., 2004). Pimecrolimus (Elidil®) is effective in treating mild-to-moderate forms of AD and is available in a 1% cream. Tacrolimus (Protopic®) is used in treating moderate-to-severe AD and is available in 0.03% and 0.1% ointments (Hanifin et al., 2004). The 0.1% tacrolimus ointment is indicated for patients older than 16 years of age (Paller, 2004). All topical calcineurin inhibitors are applied twice a day and can be used along with topical corticosteroids. Some clinicians may choose to initiate treatment of atopic dermatitis with topical corticosteroids and make a transition to topical calcineurin inhibitors when the extent of the inflammation is reduced. Others have layered these products together by applying the steroid first, applying the topical calcineurin inhibitor 30 minutes later, and decreasing the potency of the steroid or eliminate it all together once clinical improvement is seen (Paller et al., 2005).

Studies have shown that tacrolimus 0.1% is either equal to or more efficacious than a Class 5 corticosteroid in treating AD, and tacrolimus 0.03% is more efficacious than a low-potency steroid, but not as efficacious as a mid-potency topical steroid (Beck, 2005). Studies comparing tacrolimus and pimecrolimus demonstrated that 0.1% tacrolimus is more efficacious than pimecrolimus; 0.03% tacrolimus has equal efficacy to 1% pimecrolimus in mild disease; and 0.03% tacrolimus is better than 1% pimecrolimus in decreasing the itch associated with AD (Paller et al., 2005). Tacrolimus has a faster onset of action as compared to pimecrolimus, with improvement in symptoms during the first week of therapy (Paller, 2004).

Both of these medications were proven safe and effective (up to 1 year in all and 4 years in tacrolimus 0.1%) in numerous trials (Chapman et al., 2005; Darsow et al., 2005; Hanifin et al., 2005; Koo et al., 2005; Leung et al., 2004; Paller, 2004; Paller et al., 2005). These medications do not have the side effect profile of topical steroids, and therefore can be used in areas where the epidermis is thinner such as the eyelids, face, mucous membranes, genitalia, and intertriginous areas, without the risk of skin atrophy and striae. The most frequent side effect is burning at the application site (which may be more frequent in tacrolimus); however, this symptom often improves with time and usage (Abramovits, 2005; Darsow et al., 2005). Other local side effects include itching and erythema (Chapman et al., 2005). In noncomparative trials, the incidence of cutaneous viral infections such as herpes simplex, eczema herpeticum, molluscum, varicella zoster, and warts is slightly increased in patients treated with topical calcineurin inhibitors (Hanifin et al., 2005; Koo et al., 2005). Additional side effects include flu-like symptoms, allergic reactions, asthma, cough, fever, otitis media, and headache (Hanifin et al., 2005; Koo et al., 2005).

In March of 2005, the U.S. Food and Drug Administration (FDA) issued a Public Health Advisory concerning a potential increased risk of cancer associated with topical tacrolimus and pimecrolimus. The advisory was based on animal studies and a small number of case reports of skin cancer and lymphoma in adults and children treated with topical calcineurin inhibitors. The FDA made recommendations on the use of topical calcineurin inhibitors to health care providers, patients, and caregivers, as follows (see Table 5 ). Pimecrolimus and tacrolimus should be used only as second-line agents for short-term and intermittent treatment of atopic dermatitis in patients unresponsive to, or intolerant, of other treatments. Avoid the use of pimecrolimus and tacrolimus in children younger than 2 years of age. The effect of pimecrolimus and tacrolimus on the developing immune system in infants and children is not known. In clinical studies, infants and children younger than 2 years old treated with pimecrolimus had a higher rate of upper-respiratory infections than did those treated with placebo cream. Use pimecrolimus and tacrolimus only for short periods of time, not continuously. The long-term safety of pimecrolimus and tacrolimus are unknown. Children and adults with weakened or compromised immune system should not use pimecrolimus and tacrolimus. Use the minimal amount of pimecrolimus and tacrolimus needed to control the patient symptoms. In animals, increasing the dose resulted in higher rates of cancer. The FDA will be requiring a black box warning to be placed on these medications and the development of a medication guide for tacrolimus and pimecrolimus (FDA, 2005).

The American Academy of Dermatology (AAD) issued a statement in response to the FDA that it was disappointed that the FDA took this action, despite the lack of data proving proper topical use of pimecrolimus and tacrolimus is dangerous to people (AAD, 2005). The chance of systemic exposure of these medications has been studied in various trials and shown to be minimal and transient and not associated with an increase in adverse effects (Beck, 2005). Prospective clinical studies of topical calcineurin inhibitors have not shown an increase risk of lymphoma, lymphoproliferative disease, or skin cancers (Beck, 2005). Taking into consideration that systemically administered (oral) calcineurin inhibitors, cyclosporine, and tacrolimus have demonstrated an increased risk of lymphoproliferative diseases and skin cancers in transplant patients (Beck, 2005; Darsow et al., 2005; FDA, 2005), additional long-term studies of 10 years or more will be needed to determine the safety profile of topically administered calcineurin inhibitors (FDA, 2005).

Other topical treatments for AD include coal tar, doxepin, and topical sodium cromoglicate (Hanifin et al., 2004; Stainer et al., 2005; Williams, 2005). Coal tar and coal tar derivatives have been used for decades to treat AD and have efficacy similar to a Class 7 steroid (Williams, 2005). These medications exhibit antipruritic and anti-inflammatory effects and should only be used in chronic lesions of atopic dermatitis (Leung & Bieber, 2003). Coal tar can be used as monotherapy or in combination with topical steroids. Photosensitivity and folliculitis may result from coal tar (Leung & Bieber, 2003), but the major drawback is the odor and dark color which stains clothes (Correale et al., 1999). These cosmetic disadvantages generally lead to issues with compliance (Hanifin et al., 2004). Doxepin is a topical antihistamine that is able to decrease the pruritus associated with AD within 48 hours (Williams, 2005). Concerns over its potential for cutaneous sensitization and the side effect of sedation may limit its use (Leung et al., 2004). Studies in the past regarding the effectiveness of topical cromoglicate in treating AD are inconsistent. Cromoglicate acts to prevent or reduce the release of inflammatory and chemotaxic mediators from mast cells. A recent randomized trial demonstrated that the application of cromoglicate lotion (in addition to a treatment plan of topical steroids and emollients) can improve symptoms and severity of skin lesions and decrease steroid use in children with AD as compared to the lotion vehicle. Erythema and burning at the site of application are the most common side effects of topically applied cromoglicate (Stainer et al., 2005).

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