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 Abbreviations used:
successful treatment in every situation. Furthermore,
AAD: American Academy of Dermatology
these guidelines should not be interpreted as setting AD: atopic dermatitis
a standard of care, or be deemed inclusive of all PED: prescription emollient device
proper methods of care nor exclusive of other RCT: randomized controlled trial
TCI: topical calcineurin inhibitors
methods of care reasonably directed to obtaining TCS: topical corticosteroids
the same results. The ultimate judgment regarding WWT: wet-wrap therapy
From the Division of Pediatric and Adolescent Dermatology, practice, Fairfaxn; Center of Evidence-based Dermatology,
University of California, San Diegoa; Rady Children’s Hospital, Nottingham University Hospitals National Health Service Trusto;
San Diegob; Department of Dermatology, University of Califor- Department of Dermatology, University of Alabama at
nia, San Franciscoc; Department of Dermatology, Oregon Birminghamp; National Eczema Association, San Rafaelq;
Health and Science Universityd; Department of Dermatology, American Academy of Dermatology, Schaumburgr; and
Northwestern University Feinberg School of Medicine, Department of Dermatology, Seattle Children’s Hospital.s
Chicagoe; Kaplan-Amonette Department of Dermatology, Uni- Funding sources: None.
versity of Tennessee Health Science Centerf; Department of The authors’ conflicts of interest/disclosure statements appear at
Dermatology and Skin Science, University of British Columbiag; the end of the article.
Department of Dermatology, Ann and Robert H. Lurie Chil- Accepted for publication March 13, 2014.
dren’s Hospital of Chicagoh; Ronald O. Perelman Department of Reprint requests: Wendy Smith Begolka, MBS, American Academy
Dermatology, New York University School of Medicinei; Depart- of Dermatology, 930 E Woodfield Rd, Schaumburg, IL 60173.
ment of Dermatology, Case Western University, Clevelandj; E-mail: wsmithbegolka@aad.org.
Department of Dermatology, Mayo Clinic, Rochesterk; Depart- Published online May 7, 2014.
ment of Dermatology, Wake Forest University Health Sciences, 0190-9622/$36.00
Winston-Saleml; Department of Biostatistics and Epidemiology, Ó 2014 by the American Academy of Dermatology, Inc.
University of Pennsylvania School of Medicinem; private http://dx.doi.org/10.1016/j.jaad.2014.03.023
116
,J AM ACAD DERMATOL Eichenfield et al 117
VOLUME 71, NUMBER 1
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)
the propriety of any specific therapy must be made drafting of recommendations pertinent to the topic
by the physician and the patient in light of all the area of the disclosed interest.
circumstances presented by the individual patient, An evidence-based approach was used and
and the known variability and biological behavior of evidence was obtained using a systematic search of
the disease. This guideline reflects the best available PubMed, the Cochrane Library, and the Global
data at the time the guideline was prepared. The Resources for Eczema Trials2 databases from
results of future studies may require revisions to the November 2003 through November 2012 for clinical
recommendations in this guideline to reflect new questions addressed in the previous version of this
data. guideline published in 2004,1 and 1964 through 2012
for all newly identified clinical questions. Searches
were prospectively limited to publications in the
SCOPE English language. Medical subject headings (MeSH)
This guideline addresses the management of terms used in various combinations in the literature
pediatric and adult atopic dermatitis (AD; atopic search included: ‘‘atopic dermatitis,’’ ‘‘atopic eczema,’’
eczema) of all severities. The treatment of other ‘‘topical agents,’’ ‘‘topicals,’’ ‘‘nonpharmacologic,’’
forms of dermatitis, such as irritant dermatitis and ‘‘barrier,’’ ‘‘emollient,’’ ‘‘moisturizer,’’ ‘‘bathing,’’ ‘‘oil,’’
allergic contact dermatitis in those without AD, are ‘‘topical corticosteroid,’’ ‘‘hydrocortisone,’’ ‘‘calci-
outside the scope of this document. neurin inhibitor,’’ ‘‘tacrolimus,’’ ‘‘pimecrolimus,’’
Recommendations on AD treatment and manage- ‘‘coal tar,’’ ‘‘phosphodiesterase inhibitors,’’ ‘‘antimi-
ment are subdivided into 4 sections given the signif- crobial,’’ ‘‘antiseptic,’’ ‘‘retapamulin,’’ ‘‘triclosan,’’
icant breadth of the topic, and to update and expand ‘‘chlorhexidine,’’ ‘‘beta-thujaplicin,’’ ‘‘mupirocin,’’ ‘‘tri-
on the clinical information and recommendations clocarban,’’ ‘‘antibacterial soap,’’ ‘‘topical antibiotic,’’
previously published in 2004.1 This document is the ‘‘pseudomonic acid,’’ and ‘‘potassium
second part of the series and covers the use of permanganate.’’
nonpharmacologic approaches (eg, moisturizers, A total of 1789 abstracts were initially assessed for
bathing practices, and wet wraps), along with phar- possible inclusion. After removal of duplicate data,
macologic topical modalities, including corticoste- 246 were retained for final review based on rele-
roids, calcineurin inhibitors, antimicrobials, and vancy and the highest level of available evidence
antihistamines. for the outlined clinical questions. Evidence tables
were generated for these studies and used by the
METHOD work group in developing recommendations. The
A work group of recognized AD experts was American Academy of Dermatology’s (AAD’s) prior
convened to determine the audience and scope of published guidelines on AD were also evaluated, as
the guideline, and to identify important clinical were other current published guidelines on AD.1,3-5
questions in the use of topical therapies for AD The available evidence was evaluated using a
management (Table I). Work group members unified system called the Strength of Recommenda-
completed a disclosure of interests that was updated tion Taxonomy developed by editors of the US
and reviewed for potential relevant conflicts of family medicine and primary care journals (ie,
interest throughout guideline development. If a American Family Physician, Family Medicine,
potential conflict was noted, the work group mem- Journal of Family Practice, and BMJ USA).6
ber recused himself or herself from discussion and Evidence was graded using a 3-point scale based
, 118 Eichenfield et al J AM ACAD DERMATOL
JULY 2014
on the quality of study methodology (eg, random- they address different aspects of AD pathogenesis.
ized control trial [RCT ], case-control, prospective/ Each class of treatment is discussed in regards to its
retrospective cohort, case series), and the overall mode of action and main use in therapy, and where
focus of the study (ie, diagnosis, treatment/preven- possible, suggestions on dosing and monitoring are
tion/screening, or prognosis) as follows: given based on available evidence.
I. Good-quality patient-oriented evidence (ie,
evidence measuring outcomes that matter to
patients: morbidity, mortality, symptom NONPHARMACOLOGIC INTERVENTIONS
improvement, cost reduction, and quality of life). Moisturizers
II. Limited-quality patient-oriented evidence. Xerosis is one of the cardinal clinical features of
III. Other evidence including consensus guidelines, AD and results from a dysfunctional epidermal
opinion, case studies, or disease-oriented evi- barrier. Topical moisturizers are used to combat
dence (ie, evidence measuring intermediate, phys- xerosis and transepidermal water loss, with tradi-
iologic, or surrogate end points that may or may tional agents containing varying amounts of emol-
not reflect improvements in patient outcomes). lient, occlusive, and/or humectant ingredients.
Although they often include water as well, this only
Clinical recommendations were developed based
delivers a transient effect, whereas the other com-
on the best available evidence tabled in the guide-
ponents provide the main benefits.8 Emollients (eg,
line. These are ranked as follows:
glycol and glyceryl stearate, soy sterols) lubricate
A. Recommendation based on consistent and good-
and soften the skin, occlusive agents (eg, petrolatum,
quality patient-oriented evidence.
dimethicone, mineral oil) form a layer to retard
B. Recommendation based on inconsistent or
evaporation of water, whereas humectants (eg,
limited-quality patient-oriented evidence.
glycerol, lactic acid, urea) attract and hold water.
C. Recommendation based on consensus, opinion,
The application of moisturizers increases hydra-
case studies, or disease-oriented evidence.
tion of the skin, as measured subjectively by patients
In those situations where documented evidence- and objectively by assessment of capacitance or
based data were not available, expert opinion was conductance and with microscopy.8-10 In addition,
used to generate clinical recommendations. a number of clinical trials have shown that they
This guideline has been developed in accordance lessen symptoms and signs of AD, including pruritus,
with the AAD/AAD Association Administrative erythema, fissuring, and lichenification.9-13 Thus,
Regulations for Evidence-based Clinical Practice moisturizers can themselves give some reduction in
Guidelines (version approved May 2010), which inflammation and AD severity. Furthermore, their
includes the opportunity for review and comment use decreases the amount of prescription anti-
by the entire AAD membership and final review and inflammatory treatments required for disease con-
approval by the AAD Board of Directors.7 This trol, as demonstrated in 3 RCTs.13-15 Moisturizers can
guideline will be considered current for a period of be the main primary treatment for mild disease and
5 years from the date of publication, unless reaf- should be part of the regimen for moderate and
firmed, updated, or retired at or before that time. severe disease.16 They are also an important compo-
nent of maintenance treatment and prevention of
DEFINITION flares (further discussed in part 4 of these guide-
AD is a chronic, pruritic inflammatory skin disease lines). Moisturizers are therefore a cornerstone of AD
that occurs most frequently in children, but also therapy and should be included in management
affects many adults. It follows a relapsing course. AD plans (recommendations summarized in Table II and
is often associated with elevated serum immuno- level of evidence summarized in Table III).
globulin (IgE) levels and a personal or family history There is a lack of systematic studies to define an
of type I allergies, allergic rhinitis, and asthma. optimal amount or frequency of application of
Atopic eczema is synonymous with AD. moisturizers.17 It is generally thought that liberal
and frequent reapplication is necessary such that
INTRODUCTION xerosis is minimal. Traditional moisturizers are
Topical agents are the mainstay of AD therapy. formulated into a variety of delivery systems,
Even in more severe cases needing systemic or including creams, ointments, oils, gels, and lotions.
phototherapy, they are often used in conjunction Although most ointments have the advantage of not
with these modalities. Although discussed in sepa- containing preservatives, which may cause stinging
rate subsections, topical agents from several classes when applied to inflamed skin, they may be too
are frequently used in combination, in part because greasy for some patients with AD. Lotions have a