Summary Guidelines_of_care_for_the_management_of_atopic_dermatitis_section 2

FROM THE ACADEMY Guidelines of care for the management of atopic dermatitis Section 2. Management and treatment of atopic dermatitis with topical therapies Work Group: Lawrence F. Eichenfield, MD (Co-chair),a,b Wynnis L. Tom, MD,a,b Timothy G. Berger, MD,c Alfons Krol, MD,d Amy S. Paller, MS, MD,e Kathryn Schwarzenberger, MD,f James N. Bergman, MD,g Sarah L. Chamlin, MD, MSCI,h David E. Cohen, MD,i Kevin D. Cooper, MD,j Kelly M. Cordoro, MD,c Dawn M. Davis, MD,k Steven R. Feldman, MD, PhD,l Jon M. Hanifin, MD,d David J. Margolis, MD, PhD,m Robert A. Silverman, MD,n Eric L. Simpson, MD,d Hywel C. Williams, DSc,o Craig A. Elmets, MD,p Julie Block, BA,q Christopher G. Harrod, MS,r Wendy Smith Begolka, MBS,r and Robert Sidbury, MD (Co-chair)s San Diego, San Francisco, and San Rafael, California; Portland, Oregon; Chicago and Schaumburg, Illinois; Memphis, Tennessee; Vancouver, British Columbia, Canada; New York, New York; Cleveland, Ohio; Rochester, Minnesota; Winston-Salem, North Carolina; Philadelphia, Pennsylvania; Fairfax, Virginia; Nottingham, United Kingdom; Birmingham, Alabama; and Seattle, Washington Atopic dermatitis is a common and chronic, pruritic inflammatory skin condition that can affect all age groups. This evidence-based guideline addresses important clinical questions that arise in its management. In this second of 4 sections, treatment of atopic dermatitis with nonpharmacologic interventions and pharmacologic topical therapies are reviewed. Where possible, suggestions on dosing and monitoring are given based on available evidence. ( J Am Acad Dermatol 2014;71:116-32.) Key words: antihistamines; antimicrobials; atopic dermatitis; bathing; calcineurin inhibitors; corticosteroids; emollients; topicals; wet wraps. DISCLAIMER Adherence to these guidelines will not ensure successful treatment in every situation. Furthermore, these guidelines should not be interpreted as setting a standard of care, or be deemed inclusive of all proper methods of care nor exclusive of other methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding From the Division of Pediatric and Adolescent Dermatology, University of California, San Diegoa; Rady Children’s Hospital, San Diegob; Department of Dermatology, University of California, San Franciscoc; Department of Dermatology, Oregon Health and Science Universityd; Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicagoe; Kaplan-Amonette Department of Dermatology, University of Tennessee Health Science Centerf; Department of Dermatology and Skin Science, University of British Columbiag; Department of Dermatology, Ann and Robert H. Lurie Children’s Hospital of Chicagoh; Ronald O. Perelman Department of Dermatology, New York University School of Medicinei; Department of Dermatology, Case Western University, Clevelandj; Department of Dermatology, Mayo Clinic, Rochesterk; Department of Dermatology, Wake Forest University Health Sciences, Winston-Saleml; Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicinem; private practice, Fairfaxn; Center of Evidence-based Dermatology, Nottingham University Hospitals National Health Service Trusto; Department of Dermatology, University of Alabama at Birminghamp; National Eczema Association, San Rafaelq; American Academy of Dermatology, Schaumburgr; and Department of Dermatology, Seattle Children’s Hospital.s Funding sources: None. The authors’ conflicts of interest/disclosure statements appear at the end of the article. Accepted for publication March 13, 2014. Reprint requests: Wendy Smith Begolka, MBS, American Academy of Dermatology, 930 E Woodfield Rd, Schaumburg, IL 60173. E-mail: . Published online May 7, 2014. /$36.00
2014 by the American Academy of Dermatology, Inc. Abbreviations used: AAD: American Academy of Dermatology AD: atopic dermatitis PED: prescription emollient device RCT: randomized controlled trial TCI: topical calcineurin inhibitors TCS: topical corticosteroids WWT: wet-wrap therapy 116 the propriety of any specific therapy must be made by the physician and the patient in light of all the circumstances presented by the individual patient, and the known variability and biological behavior of the disease. This guideline reflects the best available data at the time the guideline was prepared. The results of future studies may require revisions to the recommendations in this guideline to reflect new data. SCOPE This guideline addresses the management of pediatric and adult atopic dermatitis (AD; atopic eczema) of all severities. The treatment of other forms of dermatitis, such as irritant dermatitis and allergic contact dermatitis in those without AD, are outside the scope of this document. Recommendations on AD treatment and management are subdivided into 4 sections given the significant breadth of the topic, and to update and expand on the clinical information and recommendations previously published in 2004.1 This document is the second part of the series and covers the use of nonpharmacologic approaches (eg, moisturizers, bathing practices, and wet wraps), along with pharmacologic topical modalities, including corticosteroids, calcineurin inhibitors, antimicrobials, and antihistamines. METHOD A work group of recognized AD experts was convened to determine the audience and scope of the guideline, and to identify important clinical questions in the use of topical therapies for AD management (Table I). Work group members completed a disclosure of interests that was updated and reviewed for potential relevant conflicts of interest throughout guideline development. If a potential conflict was noted, the work group member recused himself or herself from discussion and drafting of recommendations pertinent to the topic area of the disclosed interest. An evidence-based approach was used and evidence was obtained using a systematic search of PubMed, the Cochrane Library, and the Global Resources for Eczema Trials2 databases from November 2003 through November 2012 for clinical questions addressed in the previous version of this guideline published in 2004,1 and 1964 through 2012 for all newly identified clinical questions. Searches were prospectively limited to publications in the English language. Medical subject headings (MeSH) terms used in various combinations in the literature search included: ‘‘atopic dermatitis,’’ ‘‘atopic eczema,’’ ‘‘topical agents,’’ ‘‘topicals,’’ ‘‘nonpharmacologic,’’ ‘‘barrier,’’ ‘‘emollient,’’ ‘‘moisturizer,’’ ‘‘bathing,’’ ‘‘oil,’’ ‘‘topical corticosteroid,’’ ‘‘hydrocortisone,’’ ‘‘calcineurin inhibitor,’’ ‘‘tacrolimus,’’ ‘‘pimecrolimus,’’ ‘‘coal tar,’’ ‘‘phosphodiesterase inhibitors,’’ ‘‘antimicrobial,’’ ‘‘antiseptic,’’ ‘‘retapamulin,’’ ‘‘triclosan,’’ ‘‘chlorhexidine,’’ ‘‘beta-thujaplicin,’’ ‘‘mupirocin,’’ ‘‘triclocarban,’’ ‘‘antibacterial soap,’’ ‘‘topical antibiotic,’’ ‘‘pseudomonic acid,’’ and ‘‘potassium permanganate.’’ A total of 1789 abstracts were initially assessed for possible inclusion. After removal of duplicate data, 246 were retained for final review based on relevancy and the highest level of available evidence for the outlined clinical questions. Evidence tables were generated for these studies and used by the work group in developing recommendations. The American Academy of Dermatology’s (AAD’s) prior published guidelines on AD were also evaluated, as were other current published guidelines on AD.1,3-5 The available evidence was evaluated using a unified system called the Strength of Recommendation Taxonomy developed by editors of the US family medicine and primary care journals (ie, American Family Physician, Family Medicine, Journal of Family Practice, and BMJ USA).6 Evidence was graded using a 3-point scale based Table I. Clinical questions used to structure the evidence review for the management and treatment of atopic dermatitis with topical therapies d What is the effectiveness of nonpharmacologic interventions such as moisturizers, prescription emollient devices, bathing practices and oils, and wet wraps for the treatment of atopic dermatitis? d What are the efficacy, optimal dose, frequency of application, and adverse effects of the following agents used as monotherapy or in combination with other topical agents for the treatment of atopic dermatitis? n Topical corticosteroids n Topical calcineurin inhibitors n Topical antimicrobials/antiseptics n Topical antihistamines n Others (eg, coal tar, phosphodiesterase inhibitors) J AM ACAD DERMATOL VOLUME 71, NUMBER 1 Eichenfield et al 117 on the quality of study methodology (eg, randomized control trial [RCT ], case-control, prospective/ retrospective cohort, case series), and the overall focus of the study (ie, diagnosis, treatment/prevention/ screening, or prognosis) as follows: I. Good-quality patient-oriented evidence (ie, evidence measuring outcomes that matter to patients: morbidity, mortality, symptom improvement, cost reduction, and quality of life). II. Limited-quality patient-oriented evidence. III. Other evidence including consensus guidelines, opinion, case studies, or disease-oriented evidence (ie, evidencemeasuring intermediate, physiologic, or surrogate end points that may or may not reflect improvements in patient outcomes). Clinical recommendations were developed based on the best available evidence tabled in the guideline. These are ranked as follows: A. Recommendation based on consistent and goodquality patient-oriented evidence. B. Recommendation based on inconsistent or limited-quality patient-oriented evidence. C. Recommendation based on consensus, opinion, case studies, or disease-oriented evidence. In those situations where documented evidencebased data were not available, expert opinion was used to generate clinical recommendations. This guideline has been developed in accordance with the AAD/AAD Association Administrative Regulations for Evidence-based Clinical Practice Guidelines (version approved May 2010), which includes the opportunity for review and comment by the entire AAD membership and final review and approval by the AAD Board of Directors.7 This guideline will be considered current for a period of 5 years from the date of publication, unless reaffirmed, updated, or retired at or before that time. DEFINITION AD is a chronic, pruritic inflammatory skin disease that occurs most frequently in children, but also affects many adults. It follows a relapsing course. AD is often associated with elevated serum immunoglobulin (IgE) levels and a personal or family history of type I allergies, allergic rhinitis, and asthma. Atopic eczema is synonymous with AD. INTRODUCTION Topical agents are the mainstay of AD therapy. Even in more severe cases needing systemic or phototherapy, they are often used in conjunction with these modalities. Although discussed in separate subsections, topical agents from several classes are frequently used in combination, in part because they address different aspects of AD pathogenesis. Each class of treatment is discussed in regards to its mode of action and main use in therapy, and where possible, suggestions on dosing and monitoring are given based on available evidence. NONPHARMACOLOGIC INTERVENTIONS Moisturizers Xerosis is one of the cardinal clinical features of AD and results from a dysfunctional epidermal barrier. Topical moisturizers are used to combat xerosis and transepidermal water loss, with traditional agents containing varying amounts of emollient, occlusive, and/or humectant ingredients. Although they often include water as well, this only delivers a transient effect, whereas the other components provide the main benefits.8 Emollients (eg, glycol and glyceryl stearate, soy sterols) lubricate and soften the skin, occlusive agents (eg, petrolatum, dimethicone, mineral oil) form a layer to retard evaporation of water, whereas humectants (eg, glycerol, lactic acid, urea) attract and hold water. The application of moisturizers increases hydration of the skin, as measured subjectively by patients and objectively by assessment of capacitance or conductance and with microscopy.8-10 In addition, a number of clinical trials have shown that they lessen symptoms and signs of AD, including pruritus, erythema, fissuring, and lichenification.9-13 Thus, moisturizers can themselves give some reduction in inflammation and AD severity. Furthermore, their use decreases the amount of prescription antiinflammatory treatments required for disease control, as demonstrated in 3 RCTs.13-15 Moisturizers can be the main primary treatment for mild disease and should be part of the regimen for moderate and severe disease.16 They are also an important component of maintenance treatment and prevention of flares (further discussed in part 4 of these guidelines). Moisturizers are therefore a cornerstone of AD therapy and should be included in management plans (recommendations summarized in Table II and level of evidence summarized in Table III). There is a lack of systematic studies to define an optimal amount or frequency of application of moisturizers.17 It is generally thought that liberal and frequent reapplication is necessary such that xerosis is minimal. Traditional moisturizers are formulated into a variety of delivery systems, including creams, ointments, oils, gels, and lotions. Although most ointments have the advantage of not containing preservatives, which may cause stinging when applied to inflamed skin, they may be too greasy for some patients with AD. Lotions have a J AM ACAD DERMATOL JULY 2014 118 Eichenfield et al higher water content that can evaporate and may be less ideal in those with significant xerosis. Prescription emollient devices (PEDs) are a newer class of topical agents designed to target specific defects in skin barrier function observed in AD. They include preparations having distinct ratios of lipids that mimic endogenous compositions and creams containing palmitoylethanolamide, glycyrrhetinic acid, or other hydrolipids. They are generally recommended for 2 or 3 times daily use depending on the specific agent. Although there is some evidence that PEDs also lessen symptoms and signs of AD, including xerosis and inflammation, they have only been tested in a small number of controlled studies.16,18-20 They are approved as 510(k) medical devices based on the assertion that they serve a Table II. Recommendations for nonpharmacologic interventions for the treatment of atopic dermatitis The application of moisturizers should be an integral part of the treatment of patients with AD as there is strong evidence that their use can reduce disease severity and the need for pharmacologic intervention. Bathing is suggested for patients with AD as part of treatment and maintenance; however, there is no standard for the frequency or duration of bathing appropriate for those with AD. Moisturizers should be applied soon after bathing to improve skin hydration in patients with AD. Limited use of nonsoap cleansers (that are neutral to low pH, hypoallergenic, and fragrance free) is recommended. For the treatment of patients with AD, the addition of oils, emollients, and most other additives to bath water and the use of acidic spring water cannot be recommended at this time, because of insufficient evidence. Use of wet-wrap therapy with or without a topical corticosteroid can be recommended for patients with moderate to severe AD to decrease disease severity and water loss during flares.