Treatment of Atopic Dermatitis (Eczema) William2019 PDF

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Treatment of atopic dermatitis (eczema)

Authors: William L Weston, MD, William Howe, MD
Section Editors: Robert P Dellavalle, MD, PhD, MSPH, Moise L Levy, MD, Joseph Fowler, MD
Deputy Editor: Rosamaria Corona, MD, DSc
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Apr 2019. | This topic last updated: Apr 23, 2019.
INTRODUCTION
Atopic dermatitis is a chronic, pruritic, inflammatory skin disease that occurs most frequently in
children, but also affects many adults [1]. Clinical features of atopic dermatitis include skin
dryness, erythema, oozing and crusting, and lichenification. Pruritus is a hallmark of the condition
and is responsible for much of the disease burden for patients and their families.
The goals of treatment are to reduce symptoms (pruritus and dermatitis), prevent exacerbations,
and minimize therapeutic risks. Standard treatment modalities for the management of these
patients are centered around the use of topical anti-inflammatory preparations and moisturization
of the skin, but patients with severe disease may require phototherapy or systemic treatment [2,3].
Conventional therapy for atopic dermatitis is reviewed here. The management of severe, refractory
atopic dermatitis in children and adults and the epidemiology, pathogenesis, clinical
manifestations, and diagnosis of atopic dermatitis are discussed separately.
● (See "Management of severe atopic dermatitis (eczema) in children".)

● (See "Evaluation and management of severe refractory atopic dermatitis (eczema) in adults".)
● (See "Atopic dermatitis (eczema): Pathogenesis, clinical manifestations, and diagnosis".)
GENERAL APPROACH
The optimal management of atopic dermatitis requires a multipronged approach that involves the
elimination of exacerbating factors, restoration of the skin barrier function and hydration of the
skin, patient education, and pharmacologic treatment of skin inflammation (algorithm 1) [4].
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Elimination of exacerbating factors — Exacerbating factors in atopic dermatitis that disrupt an

already abnormal epidermal barrier include excessive bathing without subsequent moisturization,
low humidity environments, emotional stress, xerosis (dry skin), overheating of skin, and exposure
to solvents and detergents [5,6]. Avoiding these situations is helpful for acute flares as well as for
long-term management. Since atopic individuals tend to respond more readily to pruritic stimuli,
anything that tends to induce itch in an individual should be avoided.
Adjunctive measures that can be useful in all patients with dermatitis include [7]:
● Avoid trigger factors such as heat, low humidity
● Treat skin infections such as Staphylococcus aureus and herpes simplex (see 'Management
of infection' below)
● Use antihistamines for sedation and control of itching (see 'Controlling pruritus' below)
● Treat stress and anxiety
Aeroallergens and food allergens — There is controversy regarding whether environmental

or food allergies are exacerbating factors in patients with atopic dermatitis. (See "Role of allergy in
atopic dermatitis (eczema)".)
Hypersensitivity to house dust mites (eg, Dermatophagoides pteronyssinus, D. farinae), animal

danders, molds, and pollens is thought to be associated with flares of atopic dermatitis [8,9].
However, although many atopic dermatitis patients are sensitized to house dust mites, reduction
of house dust mite antigens in the atopic patient's environment does not seem to be useful for
disease control [10,11].
There is a lack of evidence that dietary interventions are helpful in reducing the severity or
preventing flares of atopic dermatitis in unselected patients. Although approximately 50 percent of
children with atopic dermatitis may have positive skin prick tests or specific IgE to one or more
food allergens (in particular, cow's milk, egg, wheat, and peanut), food sensitization is clinically
irrelevant in most cases [12]. A systematic review of nine randomized trials including 421 children
and adults with atopic eczema indicates that either milk and egg exclusion, a few-foods diet, or an
elemental diet are not beneficial in unselected patients with atopic dermatitis [13]. One study
suggests that an egg-free diet may be helpful for infants with proven sensitivity to eggs [14].
Contact allergens — Atopic individuals are at an increased risk for developing allergic contact
dermatitis (ACD) to nickel as well as many components of topical treatments (eg, fragrances,
preservatives, neomycin) [15,16]. ACD should be suspected when patients do not respond to
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appropriate topical therapy or when affected areas continue to spread beyond the usual flexural
locations.
Maintaining skin hydration
Emollients and moisturizers — Skin hydration is a key component of the overall

management of patients with atopic dermatitis. Lotions, which have a high water and low oil
content, can worsen xerosis via evaporation and trigger a flare of the disease. In contrast, thick
creams, which have a low water content, or ointments (eg, petroleum jelly), which have zero water
content, better protect against xerosis, but some patients may complain that they are greasy. To
maintain skin hydration, emollients should be applied at least two times per day and immediately
after bathing or hand-washing.
Since atopic skin is deficient in stratum corneum lipids (especially ceramide) and "natural
moisturizing factor" (a mixture of hygroscopic amino acids resulting from filaggrin breakdown),
moisturizers that contain those ingredients may be beneficial. There are a number of topical
moisturizers available in the United States by prescription. These agents contain a variety of
components intended to improve skin barrier function and are expensive. There are few data
demonstrating their efficacy, but one randomized trial suggests that they are no more effective
than over-the-counter emollients [17].
A 2017 systematic review of 77 studies including 6603 participants (mean age 19 years) with
mostly mild to moderate eczema evaluated the efficacy of emollients and moisturizers in reducing
the signs and symptoms of eczema and the frequency of flares [18,19]:
● Based on both physician and patient assessment, the use of any moisturizers reduced
eczema severity and itch compared with no use, resulted in fewer flares, and reduced the
need for topical corticosteroids.
● In three studies, patients found that a moisturizer containing glycyrrhetinic acid (a natural
anti-inflammatory agent) was four times more effective than vehicle in reducing eczema
severity.
● In four studies, patients using a cream containing urea (a humectant agent) reported
improvement more often than those using a control cream without urea.
● Three studies assessed a moisturizer containing glycerol (a humectant agent) versus control.
More patients in the glycerol group experienced skin improvement, both by physician and
patient assessment.
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● Four studies examined oat-containing moisturizers versus no treatment or control. No

significant difference in skin improvement was noted between groups, although patients
using oat moisturizers tended to have fewer flares and reduced need for topical
corticosteroids.
Emollients are best applied immediately after bathing when the skin is well hydrated.
Bathing practices — Warm soaking baths or showers using mild or soap-free cleansers
should be part of the routine skin care for patients with atopic dermatitis. Some controversy exists
concerning the frequency of bathing and whether showering or bathing is preferable in patients
with atopic dermatitis [20-22]. Most experts recommend a hydrating bath followed by immediate
emollient application, but others recommend a shower of short duration. No well-designed studies
have been published to address this controversy. We feel that either option is reasonable but
suggest bathing to most patients. Whether bath or shower is preferred, rapid application of
emollients and/or prescribed topical preparations immediately after is important.
We do not support the use of bath additives for atopic dermatitis. However, despite a lack of high-
quality studies providing evidence of benefit, bath emollient additives (eg, liquid paraffin, oils with
or without emulsifiers, colloidal oatmeal) are widely used to improve skin hydration in children and
adults with atopic dermatitis, especially in Europe, where their use is supported by national and
international guidelines [23,24]. In the United States, while the American Academy of Allergy,
Asthma, and Immunology's practice parameter for atopic dermatitis supports the use of bath
additives, the American Academy of Dermatology guidelines recommend against them [2,25].
A large, well-designed, pragmatic, randomized trial demonstrated that emollient bath additives
provide no additional benefits beyond standard care in the management of atopic dermatitis
[26,27]. In this study, 463 children aged 1 to 11 years with mild to moderate atopic dermatitis were
assigned to use bath emollient additives or no bath additives, in addition to standard care (ie,
leave-on emollients and topical corticosteroids as needed) for 52 weeks. The primary outcome
was eczema severity assessed weekly by the patient-oriented eczema measure (POEM) over 16
weeks. At 16 weeks, there was no significant difference between the mean POEM score in the
bath additives group and that in the no bath additives group (7.5 versus 8.4). After adjusting for
potential confounders (eg, baseline severity, use of topical corticosteroids, use of soap
substitutes), the POEM score in the no bath additives group was 0.41 (95% CI -0.27 to 1.10)
points higher than in the bath additives group, which is markedly lower than the accepted minimal
clinically important difference of three points [28,29]. Similar results were obtained at 52 weeks.
Controlling pruritus — Oral H1 antihistamines are widely used as a therapeutic adjunct in

patients with atopic dermatitis to alleviate pruritus [30]. The evidence supporting their use is
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relatively weak since no large, randomized, placebo-controlled trials with definitive conclusions
have been performed. Nevertheless, first-generation, sedating antihistamines (eg,
diphenhydramine, hydroxyzine, and cyproheptadine) may be beneficial for patients with disturbed
sleep secondary to itch, although optimal doses and length of treatment have not been
determined [3].
The efficacy of second-generation, less sedating, H1 antihistamines, such as fexofenadine,

cetirizine, or loratadine, as an adjunct to topical treatment in adults and children with atopic
dermatitis remains uncertain, and their use should be limited to patients with concurrent
symptoms of urticaria or allergic rhinitis. A 2019 systematic review of 25 randomized trials, most of
which were of low methodologic quality, did not find evidence that these agents are effective in
improving the symptoms of atopic dermatitis [31]. In one of the trials including 795 children aged 1
to 2 years with eczema, cetirizine 0.5 mg/kg per day for 18 months was no more effective than
placebo in reducing the score of atopic dermatitis (SCORAD) score (from 24.9 to 15.2 in the
cetirizine group and from 25.1 to 15.7 in the placebo group) [32]. Another study including 400
adult patients with atopic dermatitis found that fexofenadine 120 mg daily for one week reduced
patient-assessed pruritus more than placebo, although the reduction was probably not clinically
significant (mean change -0.75 in the fexofenadine group versus -0.5 in the placebo group on a
pruritus scale of 0 to 8) [33].
Topical doxepin, a tricyclic antidepressant with potent H1 and H2 blocking properties, may be
used as a second-line treatment if others fail [34]. However, allergic contact dermatitis to this
agent is common [35]. Topical calcineurin inhibitors appear to be effective in controlling pruritus.
In a meta-analysis of 22 randomized trials including 481 adult patients, pimecrolimus 1% cream or
tacrolimus 0.03% to 0.1% ointment were more effective than vehicle in reducing pruritus (odds
ratio [OR] 0.64, 95% CI 0.61-0.68) [36].
Tepid baths to hydrate and cool the skin can also temporarily relieve itching. Wet dressings (wet
wraps) help soothe the skin, reduce pruritus, reduce redness, débride crusts, and limit access to
the skin. Emollients are applied to the skin, and dampened cotton garments are worn over the
affected area and covered with a dry garment [37]. The patient may use these dressings overnight
if tolerated or change them every few hours during the day. Anti-pruritic ingredients such as
phenol, menthol, and camphor are found in some moisturizers. (See "Pruritus: Overview of
management".)
Patient education — Patient education is an important component of the management of atopic

dermatitis. A systematic review of nine randomized trials (2003 participants) of educational
interventions for atopic dermatitis suggests that children and their parents or caregivers may
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benefit from structured education provided by nurses or multidisciplinary teams [38]. In the largest
of these trials including 992 children and adolescents with atopic dermatitis and their families, a
six-week education program was compared with no intervention [39]. The program consisted of
two-hour weekly sessions covering medical, nutritional, and psychological issues, and were
carried out by a multiprofessional team of dermatologists or pediatricians, psychologists, and
dietitians. After one year, the decrease in the total severity SCORAD was greater in the
intervention group than in the control group. There was also a significant improvement in
subjective assessment of severity, itching behavior, and emotional coping.
ASSESSMENT OF SEVERITY
For the management of the individual patient, it is important that clinicians evaluate the extent and
characteristics of the rash (eg, presence of erythema, excoriations, oozing, lichenification, clinical
signs of bacterial superinfection) and ask general questions about itch, sleep, impact on daily
activities, and persistence of disease [40]. Several disease severity scales (eg, the SCORAD
index, the eczema area and severity index [EASI], and the patient-oriented eczema measure
[POEM]) and patient quality of life measurement scales have been tested and validated for use in
clinical trials, but they are not commonly used in clinical practice [40]. However, POEM, which
asks about the frequency of seven symptoms (itch, sleep disturbance, dryness, flaking, weeping
or oozing, bleeding, and cracking) in the previous seven days, typically takes less than two
minutes to complete and is available from the Centre of Evidence Based Dermatology [41].
A practical guide to visual assessment of eczema severity that also includes the evaluation of
disease impact on quality of life and psychosocial wellbeing has been proposed by the United
Kingdom National Institute for Health and Care excellence:
● Mild – Areas of dry skin, infrequent itching (with or without small areas of redness); little
impact on everyday activities, sleep, and psychosocial wellbeing
● Moderate – Areas of dry skin, frequent itching, redness (with or without excoriation and
localized skin thickening); Moderate impact on everyday activities and psychosocial
wellbeing, frequently disturbed sleep
● Severe – Widespread areas of dry skin, incessant itching, redness (with or without
excoriation, extensive skin thickening, bleeding, oozing, cracking, and alteration of
pigmentation); severe limitation of everyday activities and psychosocial functioning, nightly
loss of sleep
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PATIENTS WITH MILD TO MODERATE DISEASE
Initial treatment — Topically applied corticosteroids and emollients are the mainstay of therapy
for atopic dermatitis (algorithm 1) [2]. The choice of the corticosteroid potency should be based
upon the patient's age, body area involved, and degree of skin inflammation. Topical calcineurin
inhibitors may be an alternative to topical corticosteroids, in particular for the treatment of the
face, including the eyelids, neck, and skin folds.
Topical corticosteroids — For patients with mild atopic dermatitis, we suggest a low potency
(groups five and six (table 1)) corticosteroid cream or ointment (eg, desonide 0.05%,
hydrocortisone 2.5%) (algorithm 1). Topical corticosteroids are applied one or two times per day
for two to four weeks. Emollients should be liberally used multiple times per day in conjunction
with topical corticosteroids. Emollients can be applied before or after topical corticosteroids [42].
(See 'Emollients and moisturizers' above.)
For patients with moderate disease, we suggest medium to high potency (groups three and four
(table 1)) corticosteroids (eg, fluocinolone 0.025%, triamcinolone 0.1%, betamethasone
dipropionate 0.05%). In patients with acute flares, super high or high potency topical
corticosteroids (group one to three (table 1)) can be used for up to two weeks and then replaced
with lower potency preparations until the lesions resolve.
The face and skin folds are areas that are at high risk for atrophy with corticosteroids. Initial
therapy in these areas should start with a low potency steroid (group VI (table 1)), such as
desonide 0.05% ointment. High potency topical corticosteroids are generally avoided in skin folds
and on the face; however, limited brief use (five to seven days) of potent corticosteroids may
produce a rapid response after which patients can be switched to lower potency preparations.
Maintenance therapy that includes intermittent use of a topical corticosteroid or a topical

calcineurin inhibitor may help prevent relapse. (See 'Maintenance and prevention of relapses'
below.)
Efficacy and adverse effects — A systematic review of randomized trials identified 83

studies of topical corticosteroids for atopic dermatitis [43]. Although studies were of poor
methodologic quality and short duration (<4 weeks), all indicated a large therapeutic efficacy of
topical corticosteroids compared with placebo. No clear benefit has been demonstrated with more
than once daily application [44-46].
Long-term use of topical corticosteroids, especially high or super high potency preparations, on
large body areas may lead to adrenal suppression. Other adverse effects include skin thinning,
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telangiectasias, folliculitis, and contact dermatitis. (See "General principles of dermatologic

therapy and topical corticosteroid use", section on 'Side effects'.)
Topical calcineurin inhibitors — Topical calcineurin inhibitors are nonsteroidal

immunomodulating agents that, unlike topical corticosteroids, do not cause skin atrophy or other
corticosteroid adverse effects. They can be used as an alternative to topical corticosteroids for the
treatment of mild to moderate atopic dermatitis involving the face, including the eyelids, neck, and
skin folds [47,48].
Tacrolimus ointment and pimecrolimus cream are applied twice a day. Tacrolimus comes in two
strengths; the 0.1% formulation is appropriate initial therapy for adults, and the 0.03% formulation
is appropriate for children and for adults who do not tolerate the higher dose. In patients who do
not tolerate tacrolimus because of burning or stinging, pimecrolimus may be better tolerated.
Both tacrolimus and pimecrolimus topical preparations are approved by the US Food and Drug
Administration (FDA) for use in children over the age of two years. However, concerns have been
raised by the FDA about a possible link to cancers, in particular lymphoma and skin cancer
[49,50]. (See 'Long-term safety concerns' below.)
Efficacy and minor side effects — Topical calcineurin inhibitors are generally recognized
as being equal in strength to medium potency (groups four and five (table 1)) topical steroids, and
should be considered a second-line therapy [51]. In addition to its inhibitory effect on cytokine
production, topical tacrolimus causes alterations in epidermal antigen-presenting dendritic cells
that may result in decreased immunologic response to antigens [52]. Pimecrolimus 1% cream is a
calcineurin inhibitor like tacrolimus that was developed specifically to treat inflammatory skin
conditions. Its mechanism of action is similar to topical tacrolimus, and it does not appear to have
systemic immune effects [53]. Transient burning, erythema, and pruritus are the most common
adverse effects [54].
The efficacy of tacrolimus has been demonstrated in several randomized trials and systematic
reviews [47,55,56]. Tacrolimus ointment, particularly the 0.1% preparation, may be more effective
than pimecrolimus cream, although it may also cause greater local irritation.
● A meta-analysis of 25 randomized trials including 6897 patients showed that tacrolimus 0.1%
was more effective than vehicle for the treatment of patients with moderate to severe atopic
dermatitis (44 percent of patients in the tacrolimus group improved by greater than 90
percent, versus 20 percent in the vehicle group) [47]. Tacrolimus was more effective than
hydrocortisone acetate and comparable in efficacy to hydrocortisone butyrate. Pimecrolimus
was more effective than vehicle in the treatment of mild to moderate atopic dermatitis (33
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percent of patients were clear or almost clear at three weeks versus 10 percent of those who
used the vehicle) and in preventing flares. Pimecrolimus was less effective than
betamethasone valerate, but its potency compared with hydrocortisone was not evaluated in
any of the included trials.
● A subsequent meta-analysis of four randomized trials comparing tacrolimus with

pimecrolimus for the treatment of atopic dermatitis, including more than 1800 patients, found
that tacrolimus 0.1% ointment was more effective than pimecrolimus 1% cream after
six weeks of therapy in adult patients (relative risk 0.58, 95% CI 0.46-0.72) [56]. In pediatric
patients with moderate to severe eczema, tacrolimus 0.03% was superior to pimecrolimus 1%
(relative risk 0.65, 95% CI 0.57-0.75). However, in the group of pediatric patients with mild to
moderate eczema, there was no significant difference between tacrolimus 0.03% and 1%
pimecrolimus.
● In a systematic review of 31 randomized trials, pimecrolimus was significantly better than

vehicle in preventing flares at six months [57]. However, pimecrolimus was less effective than
medium potency topical corticosteroids (triamcinolone acetonide 0.1% and betamethasone
valerate 0.1%) and tacrolimus 0.1%.
Long-term safety concerns — Although in controlled trials the topical calcineurin inhibitors
have appeared to be safe in adults and children [54,58-61], in 2005, based upon case reports,
animal studies, and the known risks with systemic calcineurin inhibitors, the FDA issued warnings
about a possible link between the topical calcineurin inhibitors and cancer [62], and in 2006
placed a boxed warning on the prescribing information for these medications [63].
Issues of concern include:
● Animal studies in mice, rats, and monkeys have found an increased risk of lymphoma and
skin cancers with topical or oral exposure to calcineurin inhibitors.
● As of December 2004, the FDA had received 29 reports of cancers in adults and children
treated with topical calcineurin inhibitors; approximately half the cases were lymphomas and
the other half were cutaneous tumors.
● Between January 2004 and January 2009, the FDA received 46 reports of new cancer cases
among children 0 to 16 years old who used topical pimecrolimus and/or topical tacrolimus (30
lymphomas/leukemias, 8 skin cancers, and 8 other cancers).
However, no definite causal relationship has been established [64], and two case-control studies
did not detect an increased risk of lymphoma among patients treated with topical calcineurin
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inhibitors [65,66]. The Pediatric Eczema Elective Registry (PEER) is an industry-sponsored,

ongoing cohort study established in 2004 as part of the post-marketing commitments for the
approval of pimecrolimus to evaluate the risk of malignancy in children. Among 7500 children
enrolled between 2004 and 2014, five malignancies (two leukemias, one osteosarcoma, and two
lymphomas) were reported [67]. The standardized incidence ratio (SIR) based upon the age-
standardized Surveillance, Epidemiology, and End Results Program population was 1.2 (95% CI
0.5-2.8) for all malignancies, 2.9 (95% CI 0.7-11.7) for lymphoma and 2.0 (95% CI 0.5-8.2) for
leukemia. Although the excess risk of lymphoma and leukemia is not statistically significant, the
authors acknowledge that the small sample size and the resulting wide confidence interval may
not allow to exclude all risk.
A subsequent meta-analysis [68] did not find a statistically significant association between the use
of topical calcineurin inhibitors and risk of lymphoma, although an included cohort study reported
a fivefold increased risk of T cell lymphoma in patients exposed to topical tacrolimus (relative risk
5.44, 95% CI 2.51-11.79) [69].
Waiting for more reassuring data from larger studies, the following FDA recommendations seem
reasonable precautions [70,71]:
● Use these agents only as second-line therapy in patients unresponsive to or intolerant of

other treatments.
● Avoid the use of these agents in children younger than two years of age; clinical studies have
found higher rates of upper respiratory infections in children younger than two years who
were treated with pimecrolimus.
● Use these agents only for short periods of time and use the minimum amount necessary to
control symptoms; avoid continuous use.
● Avoid the use of these agents in patients with compromised immune systems.
Providers and patients will need to weigh the risks and benefits of topical calcineurin inhibitors in
comparison to those of other therapies. In particular, calcineurin inhibitors may continue to have
an important role in the management of atopic dermatitis in areas at high risk for skin atrophy
when treated with corticosteroids (eg, face) [72].
Off-label use in infants — Topical calcineurin inhibitors have been approved in the
United States as second-line therapies for the short and intermittent treatment of mild to moderate
atopic dermatitis in adults and children aged ≥2 years. However, they have been used off-label in
children as first-line treatment for atopic dermatitis, and in children <2 years, in the absence of
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long-term studies evaluating their efficacy and safety compared with low- or mid-potency topical
corticosteroids [73].
A five-year industry-sponsored randomized trial evaluated the safety and long-term efficacy of
pimecrolimus 1% cream compared with low-potency (1% hydrocortisone) or medium-potency
(0.1% hydrocortisone butyrate) topical corticosteroids in over 2400 infants 3 to 12 months of age
with mild to moderate atopic dermatitis [74]. After 5 years, overall treatment success, measured by
an investigator global assessment score, was achieved in approximately 89 percent of children in
the pimecrolimus group and 92 percent in the topical corticosteroid group. Vaccine
responsiveness, growth, immune function, and cancer rates were similar in the two groups. The
overall rates of adverse events were also similar in the two groups, although episodes of
bronchitis, infected eczema, impetigo, and nasopharyngitis were slightly more frequent in the
pimecrolimus group than in the topical corticosteroid group.
Since the rates of cutaneous adverse events (eg, skin irritation, atrophy, telangiectasias) were not
reported in this trial, the advantage of using pimecrolimus rather than low- to mid-potency topical
corticosteroids for infants with mild to moderate atopic dermatitis remains unclear.
Crisaborole — Crisaborole is a boron-based, small-molecule, topical phosphodiesterase 4

(PDE4) inhibitor that was approved by the FDA in December 2016 [75] for the treatment of mild to
moderate atopic dermatitis. Preliminary studies in adolescents and adults indicated that
crisaborole 2% ointment may improve the clinical signs of atopic dermatitis, including erythema,
excoriation, exudation, lichenification, and, in particular, pruritus [76-79]. Adverse effects of topical
crisaborole were mild and mainly limited to application site reactions (pain, paresthesia). Systemic
exposure to crisaborole has been shown to be limited even after maximal use (3 mg/cm2) [79].
Two subsequent phase 3, multicenter randomized trials (AD-301 and AD-302) were performed to
assess the efficacy and safety of topical crisaborole in patients with mild to moderate atopic
dermatitis [80]. In these trials, a total of 1522 patients ≥2 years of age were randomized to receive
crisaborole 2% ointment twice daily for 28 days. The primary efficacy end point (success) was
defined as an investigator's static global assessment (ISGA) score of 0 (clear) or 1 (almost clear)
with a two-grade or more improvement from baseline. At day 29, more patients in the crisaborole
groups than in the vehicle groups achieved success (32.8 versus 25.4 percent in AD-301 and 31.4
versus 18 percent in AD-302). Improvement was noted in pruritus, skin inflammation, excoriation,
and lichenification. Crisaborole-related adverse events occurred in 4.4 percent of patients and
were mild and limited to burning or stinging at the site of application.
The long-term safety of crisaborole was evaluated in a 48-week, open-label, extension study
including 517 patients (60 percent children) who had completed the AD-301 and AD-302 trials
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without experiencing adverse effects [81]. Patients with an ISGA score ≥2 initiated crisaborole
treatment twice daily for 28 days. Participants underwent an average of six treatment periods and
used an average of 133 g of crisaborole ointment per month. Adverse events, of which 86 percent
were mild or moderate, occurred in 10 percent of patients. The most frequently reported adverse
events were exacerbation of atopic dermatitis, burning or stinging in the application site, and
application site infection. Diarrhea or vomiting, side effects observed with oral PDE4 inhibitors,
were reported by approximately 1 to 2 percent of patients throughout the study. Rescue therapy
with topical corticosteroids or topical calcineurin inhibitors was needed by 22 and 26 percent of
children and adolescents, respectively, and 13 percent of adults.
Although crisaborole seems to be generally safe for long-term use, its efficacy remains uncertain,
due to the strong placebo effect noted in trials [80,82]. Head-to-head studies comparing
crisaborole with established therapies for atopic dermatitis are needed to better define its role in
the management of mild to moderate atopic dermatitis.
Maintenance and prevention of relapses — We suggest proactive therapy to prevent relapse in

adolescents and adults with moderate to severe (picture 1A-B) atopic dermatitis that responds to
continuous therapy with topical corticosteroids or calcineurin inhibitors (algorithm 1). After
induction of remission, we suggest intermittent therapy with moderate to high potency topical
corticosteroids (group three to five) (table 1). The steroid should be applied once daily to
previously affected skin areas for two consecutive days per week (ie, weekends) and may be
continued for up to 16 weeks. Emollients can be liberally used multiple times per day.
Flares of atopic dermatitis that occur during intermittent treatment may be treated by resuming
continuous use of topical corticosteroids or calcineurin inhibitors that have been effective for the
patient in the past. Similar strategies for proactive therapy are recommended in multiple national
and international guidelines for the management of atopic dermatitis [2,25,83-85].
In infants and young children with moderate to severe atopic dermatitis (picture 2A-B) who have
frequent flares, proactive intermittent therapy with low potency (groups six and seven) topical
corticosteroids (table 1) may be beneficial in preventing relapse [86]. The steroid should be
applied once daily to previously affected skin areas for two consecutive days per week (ie,
weekends) and may be continued for up to 16 weeks. Flares of atopic dermatitis that occur during
intermittent treatment may be treated by resuming continuous use of topical corticosteroids that
have been effective for the patient in the past.
In meta-analyses of randomized trials, proactive, intermittent therapy with moderate to high

potency corticosteroids or tacrolimus, after achieving disease control with continuous use of these
agents, was effective in reducing the risk of subsequent flares [87]. However, there were fewer
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adverse effects with corticosteroids, as illustrated below:
● In a meta-analysis of four randomized trials, topical fluticasone propionate (once daily for two
consecutive days per week for 16 weeks) reduced the risk of a subsequent flare by 54
percent (relative risk 0.46, 95% CI 0.38-0.55) [87]. No serious adverse events were reported.
● In a meta-analysis of three randomized trials, topical tacrolimus (once daily two to three days
per week for 10 to 12 months) reduced the risk of a subsequent flare by 22 percent (relative
risk 0.78, 95% CI 0.60-0.78) [87]. Adverse effects included pruritus, burning sensation, skin
infections, and bronchopneumonia. In addition, four patients developed a cancer. (See 'Long-
term safety concerns' above.)
Treatment of acute exacerbations — In adolescents and adults, an acute exacerbation of

chronic atopic dermatitis can sometimes be aborted by a short course of systemic glucocorticoids
(eg, prednisone 40 to 60 mg/day for three to four days, then 20 to 30 mg/day for three to four
days). This strategy is not recommended for infants and young children. (See "Major side effects
of systemic glucocorticoids" and "Management of severe atopic dermatitis (eczema) in children",
section on 'Systemic corticosteroids'.)
PATIENTS WITH MODERATE TO SEVERE DISEASE
Adult patients with moderate to severe atopic dermatitis that is not controlled with optimal topical
therapy may require phototherapy or systemic immunosuppressant treatment to achieve adequate
disease control (algorithm 1) [3,88,89]. Evidence on the efficacy and safety of phototherapy and
systemic immunosuppressants for children is limited. Thus, these treatments should be used only
in older children in whom other management options have failed and the disease has a significant
impact on the quality of life [90].
Phototherapy
In adults — Ultraviolet light therapy (phototherapy) with PUVA (psoralens plus ultraviolet A
radiation), broadband UVA, broadband UVB, combined UVA and UVB, narrow-band UVB, or UVA1
is a treatment option for moderate to severe atopic dermatitis that is not adequately controlled with
topical therapy [91-93]. (See "UVB therapy (broadband and narrowband)" and "Psoralen plus
ultraviolet A (PUVA) photochemotherapy" and "UVA1 phototherapy".)
We suggest narrowband UVB phototherapy rather than other forms of phototherapy for adult
patients with moderate to severe atopic dermatitis that is not controlled with topical therapy.
Phototherapy is usually administered three times per week. Topical corticosteroids can be
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continued as needed during phototherapy. Additional emollients may be necessary since

phototherapy may increase skin dryness.
Phototherapy for the treatment of moderate to severe atopic dermatitis has been evaluated in
randomized trials and systematic reviews. In a 2013 systematic review of 19 randomized trials
including 905 patients, medium dose UVA1 (30 to 60 J/cm2) and narrow-band UVB were more
effective than other phototherapy modalities in reducing the clinical signs and symptoms of atopic
dermatitis, as measured with several clinical scores [94]. However, phototherapy is expensive ($25
to $100 per treatment) and prolonged treatment may lead to an increased risk of melanoma and
nonmelanoma skin cancer [95-97].
In children — Phototherapy is not suitable for infants and young children. In older children
and adolescents with atopic dermatitis not controlled with topical therapies, narrowband UVB
phototherapy may be a therapeutic option, if available. However, the benefits of phototherapy
must be weighed against potential adverse effects. (See "Management of severe atopic dermatitis
(eczema) in children", section on 'Phototherapy'.)
Oral cyclosporine
In adults — Oral cyclosporine is a short-term treatment option for patients with moderate to
severe atopic dermatitis that is not adequately controlled with topical therapy, when phototherapy
is not available or contraindicated [88,89]. For adult patients, cyclosporine is given at dose of 3 to
5 mg/kg per day in two divided doses for six weeks. The dose is then lowered to the minimum
effective dose and maintained until stable improvement is achieved, or for up to one year. After
cyclosporine withdrawal, treatment with topical corticosteroids and emollients can be resumed.
(See 'Initial treatment' above and 'Maintenance and prevention of relapses' above.)
The efficacy of oral cyclosporine for the treatment of atopic dermatitis has been evaluated in
randomized trials and systematic reviews. In a 2013 systematic review of 34 randomized trials
including 1653 patients with moderate to severe atopic dermatitis, cyclosporine was more effective
than placebo in five trials, with a mean improvement of 50 to 95 percent in different clinical
severity scores after short-term treatment (10 day to 8 weeks) [88]. In head-to-head trials,
cyclosporine was more effective than prednisolone, intravenous immunoglobulins, and
phototherapy with UVA/UVB. Higher doses (5 mg/kg per day) lead to a more rapid response than
lower doses (2.5 to 3 mg/kg).
Side effects of cyclosporine include nephrotoxicity, hypertension, hypertrichosis, gum hyperplasia,

and increased susceptibility to serious infections. Monitoring of patients receiving cyclosporine
includes measuring blood pressure and serum creatinine every two weeks for three months,
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followed by monthly monitoring. Significant elevations of either are an indication to lower the dose
or stop treatment. (See "Pharmacology of cyclosporine and tacrolimus".)
In children — Oral cyclosporine is not recommended in infants and young children with atopic
dermatitis. In older children and adolescents, the use of cyclosporine should be reserved to the
most severe cases that failed to respond to topical treatment and where there is a significant
negative impact on quality of life. (See "Management of severe atopic dermatitis (eczema) in
children", section on 'Cyclosporine'.)
Other systemic immunosuppressants — Second-line systemic immunosuppressive agents for

the treatment of atopic dermatitis include methotrexate, azathioprine, and mycophenolate mofetil.
Their use in children and adults with severe atopic dermatitis is discussed in detail separately.
(See "Management of severe atopic dermatitis (eczema) in children" and "Evaluation and
management of severe refractory atopic dermatitis (eczema) in adults".)
Dupilumab — Dupilumab is a fully human monoclonal antibody that binds to the alpha subunit
of the interleukin (IL)-4 receptor and inhibits downstream signaling of IL-4 and IL-13, cytokines of
type 2 helper T lymphocytes (Th2) that are believed to play a key role in atopic diseases,
including asthma and atopic dermatitis. Dupilumab was approved by the US Food and Drug
Administration (FDA) in March 2017 and by the European Medicine Agency in July 2017 for the
treatment of adult patients with moderate to severe atopic dermatitis not adequately controlled
with topical prescription therapies [98,99]. In a March 2019 modification of the prescribing
information, the FDA approved dupilumab (with or without topical corticosteroids) for the treatment
of adolescents aged 12 years or older with moderate to severe atopic dermatitis whose disease is
not adequately controlled with topical prescription therapies or when those therapies are not
advisable [100].
Dupilumab was initially evaluated in four small, industry-sponsored, randomized trials in adult
patients with moderate to severe atopic dermatitis [101]. In a subsequent phase IIb, randomized
trial, 379 adult patients with chronic moderate to severe atopic dermatitis present for ≥3 years
were treated with dupilumab 300 mg once a week, 300 mg every two weeks, 200 mg every two
weeks, 300 mg every four weeks, 100 mg every four weeks, or placebo once a week for 16 weeks
[102]. The primary efficacy endpoint was the percentage change in the eczema area and severity
index (EASI) score from baseline to week 16. At 16 weeks, patients in all the dupilumab treatment
groups had a greater improvement in the EASI score compared with baseline than patients in the
placebo group. The improvement was dose-dependent, with the largest effect seen in the 300 mg
once-a-week and 300 mg every-two-weeks groups (-74 and -68 percent, respectively, versus -18
percent in the placebo group). Serious treatment-related adverse events occurred in 12 of 318 (4
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percent) patients in the dupilumab groups combined and in 4 of 61 (7 percent) in the placebo
group. In an analysis of patient-reported outcomes, dupilumab was also associated with a dose-
dependent improvement in pruritus, sleep, symptoms of anxiety and depression, and health-
related quality of life [103].
The efficacy of dupilumab 300 mg or placebo given by subcutaneous injection weekly or every
other week was also evaluated in two phase III trials of identical design, SOLO1 and SOLO2,
which included 671 and 708 adult patients with long-standing moderate to severe atopic
dermatitis not controlled by topical treatments, respectively [104]. The primary endpoint was the
proportion of patients with an investigator general assessment (IGA) score of 0 or 1 (clear or
almost clear) and a reduction from baseline of at least two points in the score at week 16. The
secondary endpoint was the proportion of patients who achieved at least a 75 percent
improvement from baseline in the eczema area and severity index (EASI-75). At week 16, more
patients in the dupilumab groups than in the placebo groups achieved the primary endpoint
(approximately 40 versus 10 percent). There were no differences between trials and between
weekly or biweekly dupilumab regimens. EASI-75 was achieved by 44 to 52 percent of patients
receiving dupilumab versus 12 and 15 percent of those receiving placebo. Rescue treatment was
required in approximately 50 percent of patients receiving placebo and 15 to 20 percent of those
receiving dupilumab. Serious adverse events were rare in all groups; however, injection-site
reactions and conjunctivitis occurred more frequently in the dupilumab groups than in the placebo
group. Exacerbation of atopic dermatitis was reported overall in three patients receiving
dupilumab and in eight receiving placebo.
The results of these trials indicate that dupilumab may be an alternative systemic therapy for
long-standing atopic dermatitis in adults, despite the relatively low proportion of patients achieving
complete or near-complete clearance after 16 weeks of treatment. The long-term efficacy and
safety of dupilumab was subsequently evaluated in a randomized, double-blind, multicenter trial
(LIBERTY AD CHRONOS) [105]. In this study, 740 patients were treated with dupilumab 300 mg
once weekly, dupilumab 300 mg every 2 weeks, or placebo for 52 weeks. All patients received
concurrent treatment with topical corticosteroids (or topical calcineurin inhibitors, if indicated) and
were allowed to receive rescue treatments (topical or systemic medications or phototherapy) after
two weeks of dupilumab. The two coprimary endpoints were the proportion of patients with both
an IGA score of 0/1 (clear/almost clear) or two-point or higher reduction from baseline at week 52,
and the proportion of patients achieving EASI-75 from baseline to week 52. At week 52, more
patients in the dupilumab plus topical corticosteroids groups achieved the IGA endpoint and
EASI-75 compared with those receiving placebo plus topical corticosteroids (approximately 40
versus 13 percent, and 65 versus 22 percent, respectively). The rates of adverse events were
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similar in the three groups (83 to 88 percent). Serious adverse events occurred less frequently in
the dupilumab plus topical corticosteroids groups than in the placebo plus topical corticosteroids
group (7 and 16 percent, respectively); however, patients in the dupilumab groups experienced an
approximately twofold higher frequency of eye disorders and noninfectious conjunctivitis. The
results of this study support the use of dupilumab for the treatment of moderate to severe atopic
dermatitis in adult patients who do not respond to topical therapies alone and in whom other
systemic treatments are contraindicated.
PATIENTS WITH SEVERE REFRACTORY DISEASE
The management of severe refractory atopic dermatitis in children and adults is discussed
separately. (See "Management of severe atopic dermatitis (eczema) in children" and "Evaluation
and management of severe refractory atopic dermatitis (eczema) in adults".)
MANAGEMENT OF INFECTION
Patients with atopic dermatitis are at increased risk for cutaneous bacterial, viral, and fungal
infections. Clinical signs of bacterial superinfection, most often from S. aureus, include weeping,
pustules (picture 3), honey-colored crusting (picture 4), worsening of dermatitis, or failure to
respond to therapy. The presence of vesicles and punched-out erosions may be a sign of eczema
herpeticum.
Staphylococcus aureus — S. aureus is a frequent skin colonizer in patients with atopic

dermatitis. A meta-analysis of 95 observational studies found that 70 percent of patients with
atopic dermatitis carried S. aureus on lesional skin (95% CI 66-74) and 39 percent on the
nonlesional skin (95% CI 31-47) [106]. However, in patients without frank clinical infection, the role
of staphylococcal colonization in driving the disease severity is still unclear, although multiple
lines of evidence indicate that a relationship between heavy colonization and eczema severity
does exist [107]. An analysis of data from studies including patients with mild or severe atopic
dermatitis found a pooled colonization rate of 43 percent (95% CI 31-57) in patients with mild
atopic dermatitis, compared with 83 percent (95% CI 74-89) in those with severe atopic dermatitis
[106].
Clinically infected skin — Because of the universal skin colonization with S. aureus in
patients with atopic dermatitis, routine skin swabs for bacteriologic culture are not recommended.
However, skin and nasal swabs may be useful for recurrent infection, infection that does not
respond to treatment, or if there is concern about antimicrobial resistance or clinical suspicion of
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unusual organisms [108].
For patients with localized clinical infection, we suggest topical mupirocin. Mupirocin 2% cream is
applied twice a day for one to two weeks. A prolonged use of topical antibiotics should be avoided
because of the risk of inducing bacterial resistance. For patients with more extensive infection, we
suggest oral antibiotic therapy with cephalosporins or penicillinase-resistant penicillins [83]. Oral
antibiotics are given for two weeks. (See "Impetigo", section on 'Treatment'.)
Clinically uninfected skin — Multiple observations indicate that in patients with atopic
dermatitis without frank clinical infection there is a relationship between the epidermal density of
S. aureus and eczema severity or flare frequency [109-111]. Since sodium hypochlorite 6%
solution (liquid chlorine bleach) has activity against S. aureus, including methicillin-resistant S.
aureus (MRSA), diluted bleach baths (obtained by adding 0.5 cup or 120 mL of 6% bleach in a
full bathtub [40 gallons or 150 L] of lukewarm water, or one-half of a teaspoon of bleach in one
gallon or four liters of lukewarm water) have been suggested as an adjunct to topical treatment
between episodes of clinical infection to reduce the cutaneous load of S. aureus and improve
symptoms [112].
However, studies evaluating the efficacy of bleach baths for atopic dermatitis have been scarce
and inconsistent [113-115]. A meta-analysis of four small randomized trials (116 participants)
found that bleach baths were not more effective than plain water baths at four weeks in
decreasing the severity of atopic dermatitis as assessed by the eczema area and severity index
(EASI) and by the body surface area involved [116]. Emollients and topical corticosteroids were
permitted in all studies. Three of the four included studies also found a decrease in S. aureus
density after both bleach and normal baths, without a significant difference between groups.
Moreover, one of the included trials found that the addition of bleach baths to topical
corticosteroids was not more effective than corticosteroids alone in reducing the skin colonization
in children with moderate to severe atopic dermatitis [117].
The results of this meta-analysis indicate that bathing per se (with or without bleach) may be
effective in reducing the skin colonization from S. aureus and improving symptoms. However,
since bleach baths are inexpensive, well tolerated, and devoid of adverse effects, we continue to
suggest their use in patients with atopic dermatitis and frequent flares of clinically infected
eczema.
The efficacy of other topical antiseptics or oral or topical antibiotics in improving the severity of
dermatitis is uncertain. A systematic review found insufficient evidence to recommend the use of
oral antibiotics for the treatment of atopic dermatitis in the absence of clinical infection [118,119].
The same review found that topical antibiotics or antiseptics reduced colonization with S. aureus
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in patients with atopic dermatitis, but could not conclude that treatment with these agents in
combination with topical corticosteroids induced greater clinical improvement than topical
corticosteroids alone. However, the systematic review primarily was based on poor quality studies,
and cannot definitively discount antimicrobial therapies for patients without overt infection.
Viral infections — Atopic dermatitis patients with lesions that are infected with herpes simplex
(called eczema herpeticum or Kaposi's varicelliform eruption) should be treated immediately with
oral antiviral therapy. Examination reveals skin with punched-out erosions, hemorrhagic crusts,
and/or vesicles (picture 5A-C). Involved skin may be pruritic or painful, and lesions may be
widespread. The diagnosis should be considered in patients who fail to respond to oral antibiotics
[120]. Cases of life-threatening dissemination have been reported, and intravenous antiviral
therapy may be necessary in severe cases [120]. (See "Treatment of herpes simplex virus type 1
infection in immunocompetent patients".)
Patients with atopic dermatitis may also develop widespread molluscum contagiosum infections
(picture 6). (See "Molluscum contagiosum".)
Fungal infections — Dermatophyte infections are more common in patients with atopic
dermatitis, and can be treated with standard regimens of topical or oral antifungals. (See
"Dermatophyte (tinea) infections".)
In addition, the Malassezia furfur yeast (a normal component of skin flora) may be an
exacerbating factor in patients with head/neck atopic dermatitis [121]. Elevated Malassezia-
specific IgE levels have been reported in these patients [121]. Treatment may result in
improvement. (See "Role of allergy in atopic dermatitis (eczema)", section on 'Malassezia'.)
IMMUNOTHERAPY
Allergen-specific immunotherapy (SIT) with dust mite extract in sensitized patients with atopic
dermatitis has been studied using both subcutaneous (SCIT) and sublingual (SLIT) administration
with conflicting results [122-125]. A meta-analysis of eight randomized trials, including 385
patients, that compared SIT (mostly using house dust mite allergens) with placebo found that
patients in the SIT group were more likely to experience treatment success, as assessed by
patients or investigators, than those in the placebo group (odds ratio [OR] 5.35, 95% CI
1.61-17.77) [126]. However, there was considerable heterogeneity among studies regarding types,
doses, and pharmaceutical preparations of allergens; treatment schedules and duration; patients'
age and disease severity; and assessment of outcome. Although this meta-analysis suggests that
SIT improves the course of atopic eczema, it is unclear which patients may benefit from this form
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of treatment. SIT may be a treatment option for patients with proven sensitization to house dust
mites (eg, positive allergen-specific test; exacerbation upon natural exposure to the allergen) and
severe eczema that is not controlled with conventional therapies [127]. (See "Subcutaneous
immunotherapy for allergic disease: Indications and efficacy".)
EXPERIMENTAL AGENTS
JAK inhibitors — Tofacitinib is an oral small-molecule Janus kinase (JAK) inhibitor approved for
the treatment of rheumatoid arthritis that blocks multiple cytokine signaling, including interleukin
(IL)-4, IL-5, and IL-13, involved in immune response and inflammation. A topical formulation of
tofacitinib has been shown to have a modest beneficial effect in the treatment of mild to moderate
plaque psoriasis [128]. The efficacy of topical tofacitinib for the treatment of atopic dermatitis has
been evaluated in a phase IIa randomized trial [129]. In this study, 69 adult patients with clinically
stable, mild to moderate atopic dermatitis were treated with tofacitinib 2% ointment or placebo
twice daily for four weeks. The primary end point was the percentage change from baseline in the
Eczema Area and Severity Index (EASI). At week 4, the mean percentage change from baseline in
the EASI score was significantly greater in patients treated with topical tofacitinib than in those
treated with placebo (-82 and -30 percent, respectively). Moreover, the proportion of patients with
a physician general assessment score of clear or almost clear was higher in the tofacitinib group
than in the placebo group (73 versus 22 percent). Adverse effects, including infection, increased
blood creatine phosphokinase, and contact dermatitis, were mild and occurred in 31 percent of
patients treated with tofacitinib and 60 percent of those treated with placebo.
Although topical tofacitinib seems a promising treatment for atopic dermatitis, larger studies of
longer duration including patients with more severe disease are needed to evaluate its long-term
efficacy and safety.
Anti-IL-31 antibodies — Nemolizumab is a humanized monoclonal antibody against the receptor

A of IL-31, a newly discovered cytokine associated with chronic skin inflammation and pruritus
[130]. A phase 2 12-week randomized trial evaluated the efficacy of nemolizumab for the
treatment of adult patients with moderate to severe atopic dermatitis not controlled by topical
corticosteroids or topical calcineurin inhibitors [131]. In this study, 264 patients received
subcutaneous nemolizumab at a dose of 0.1 mg, 0.5 mg, or 2 mg per kilogram of body weight or
placebo every four weeks or nemolizumab at a dose of 2 mg per kilogram every eight weeks with
placebo given at week 4. The primary outcome was the percentage improvement from baseline in
the score on the pruritus visual-analogue scale. At 12 weeks, pruritus was reduced by 44, 60, and
63 percent in the 0.1 mg, 0.5 mg, and 2 mg groups, respectively, versus 21 percent in the
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placebo group. The body surface area affected by atopic dermatitis decreased by 8, 20, and 19
percent in the 0.1 mg, 0.5 mg, and 2 mg groups, respectively, compared with 16 percent in the
placebo group. Adverse events occurred in approximately 70 percent of patients in all study
groups and were generally mild, with the most frequent being exacerbation of atopic dermatitis
and respiratory tract infections.
Although nemolizumab appears to be a promising agent for the treatment of pruritus associated
with atopic dermatitis and the interruption of the itch-scratch cycle, larger studies of longer
durations are needed to evaluate its long-term efficacy and safety.
Anti-IL-13 antibodies — Lebrikizumab is a monoclonal antibody that binds specifically to soluble

IL-13, a pleiotropic T helper 2 cytokine that is likely to play a role in the pathogenesis of barrier
dysfunction and inflammation in atopic dermatitis, asthma, and pulmonary fibrosis [132].
Lebrikizumab has been investigated for the treatment of asthma with inconsistent results
[133-135].
In a proof-of-concept, phase 2, multicenter, randomized trial, 209 patients with moderate to severe
atopic dermatitis received subcutaneous injections of lebrikizumab 125 or 250 mg or placebo
every four weeks as an add-on to topical corticosteroid treatment [136]. At 12 weeks, more
patients in the lebrikizumab 125 mg every four weeks group achieved the primary endpoint (a 50
percent reduction in the Eczema Area and Severity Index score [EASI-50]) compared with the
placebo group (82 versus 62 percent). Lebrikizumab was generally well tolerated; nonsevere
infection was the most common adverse event and occurred with similar frequency in all groups.
The results of this study indicate that lebrikizumab in combination with topical corticosteroids may
provide some additional benefit compared with topical corticosteroids alone; however, its efficacy
as monotherapy for atopic dermatitis remains to be determined.
Anti-IL-22 antibodies — A small phase 2 randomized trial evaluated the efficacy and safety of
intravenous fezakinumab, an IL-22 antagonist, for the treatment of atopic dermatitis [137]. Sixty
adult patients with at least a six-month history of moderate to severe atopic dermatitis received
fezakinumab (a loading dose of 600 mg at baseline, followed by 300 mg every two weeks) or
placebo for 12 weeks and were followed for 8 additional weeks. At 12 and 20 weeks, the mean
Scoring of Atopic Dermatitis (SCORAD) decrease from baseline was greater in the fezakinumab
group than in the placebo group (13.8 and 18.8 points, respectively, in the fezakinumab group
versus 8 and 11.7 points, respectively, in the placebo group). Adverse events occurred with similar
frequency in the active treatment and placebo groups and were considered mild to moderate.
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UNPROVEN THERAPIES
Complementary and alternative therapies
Probiotics — Probiotic therapy with Lactobacillus and other organisms has been studied for
the treatment of atopic dermatitis in infants and children, but has proven to be of limited benefit
[138-142]. In a 2009 meta-analysis of 12 randomized trials including 781 participants, probiotics
were not more effective than placebo in reducing eczema symptoms and sleep disturbance [141].
In addition, the use of probiotics did not reduce the need for other treatments such as topical
corticosteroids. A subsequent meta-analysis of 25 randomized trials including 1600 participants,
found that probiotics were associated with a modest, clinically insignificant reduction of the
baseline scoring of atopic dermatitis (SCORAD) score (-4.5, 95% CI -6.8 to -2.2) [143].
A 2018 systematic review of 39 randomized trials (2599 participants) evaluated the efficacy of oral
live probiotics or placebo for the treatment of adults and children with mild to severe eczema
[144]. The probiotics used were bacteria of the Lactobacillus and Bifidobacteria species taken
alone or in combination with other probiotics for a period of four weeks to six months. A pooled
analysis did not show a difference between probiotics and placebo in participant- or parent-rated
severity of atopic dermatitis (mean difference in SCORAD part C [pruritus plus sleep loss] score at
the end of treatment -0.44, 95% CI -1.22 to 0.33) or quality of life. Similarly, no difference between
treatments was noted when using clinician-rated disease severity (mean difference in SCORAD
part A/B [eczema extent and intensity] -2.24, 95% CI -4.69 to 0.20). An analysis using the total
SCORAD score suggested only a modest reduction in eczema severity of uncertain clinical
significance (mean difference -3.91, 95% CI -5.86 to -1.96) in patients taking probiotics compared
with placebo. (See "Prebiotics and probiotics for treatment of allergic disease".)
Dietary supplements — Dietary supplements, including vitamins, fish oil, and plant-derived
essential fatty acids do not appear to be beneficial for the treatment of atopic dermatitis [145-147].
Evening primrose oil and borage oil, which are rich in the essential fatty acid gamma-linolenic
acid, have been widely used for the treatment of atopic dermatitis as a complementary and
alternative medicine remedy [148,149]. However, studies of supplementation of gamma-linolenic
acid for eczema have provided conflicting results [150]. A meta-analysis of 19 randomized trials of
evening primrose oil for the treatment of eczema in children and adults did not find a significant
difference in global eczema symptoms (assessed by both the participants and clinicians) between
the active treatment and the placebo group [147].
Melatonin — Melatonin is a hormone produced in the pineal gland involved in the regulation
of sleep and circadian rhythms (see "Physiology and available preparations of melatonin"). It has
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also been suggested that melatonin has antioxidant, anti-inflammatory, and immunomodulating
properties [151,152]. In children and adults with atopic dermatitis, abnormal melatonin levels have
been correlated with disease severity and degree of sleep disturbance [153-155].
In two small randomized trials, melatonin supplementation reduced disease severity and improved
sleep in children and adolescents with atopic dermatitis [156,157]:
● In a crossover trial, 48 children with atopic dermatitis involving >5 percent of the body surface
area and a history of sleep disturbance interfering with daytime activities more than three
days per week in the previous three months were treated with oral melatonin 3 mg per day or
placebo at bedtime for four weeks and then, after a washout period of two weeks, were
switched to the alternate treatment for an additional four weeks [156]. Compared with
placebo, melatonin was associated with a greater decrease from the baseline in the total
SCORAD score (-9.9 versus -0.7 points) and a greater decrease of the sleep-onset latency
time (-23 versus -1.2 minutes). No adverse effects were reported.
● Similar results were provided by another randomized trial including 70 children of 6 to 12

years of age with atopic dermatitis who received oral melatonin 6 mg or placebo an hour
before bedtime for six weeks, while continuing their usual treatment with topical
corticosteroids and emollients [157]. At the end of the study, children in the melatonin
supplementation group compared with those in the placebo group had a greater
improvement in the total SCORAD score from baseline (-6.6 versus -2.6 points) and in the
total Children's Sleep Habits Questionnaire (CSHQ) score (-5.5 versus -2.7 points), but not in
the pruritus score. A decrease in the total immunoglobulin E (IgE) level and an increase in
the total sleep time per night were also noted in the melatonin group but not in the placebo
group. No adverse effects associated with treatment were reported.
Larger studies with longer follow-up are needed to establish the role and safety of long-term
melatonin supplementation in the management of atopic dermatitis in children and adolescent.
Chinese herbal medicine — Chinese herbal medications for atopic dermatitis have been used
for many years, but their efficacy and safety have not been adequately evaluated in clinical trials
[158,159]. A systematic review found three small randomized trials and one open-label trial of a
commercial preparation of 10 traditional Chinese herbs (Zemaphyte, no longer available) [160].
Two trials showed a reduction in erythema and skin surface damage and improvement in sleep in
the active treatment group, but not in the placebo group. Another trial did not find any significant
difference between the active treatment and placebo. However, all studies were small (less than
50 patients) and had methodologic flaws. (See "Chinese herbal medicine for the treatment of
allergic diseases", section on 'Therapy for atopic dermatitis'.)
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Leukotriene receptor antagonists — Montelukast, an oral leukotriene receptor antagonist

approved for the treatment of asthma and allergic rhinitis in children and adults, has been
evaluated for the treatment of atopic dermatitis in a few randomized trials with conflicting results.
A systematic review of five randomized trials including 202 adults and children older than six
years with moderate to severe atopic dermatitis evaluated the efficacy of oral montelukast (10
mg/day in adults and 5 mg/day in children aged 6 to 14 years) given for four to eight weeks,
compared with placebo (three studies) or conventional treatment with oral antihistamines and
topical corticosteroids (two studies) [161]. The main outcome measure was a reduction in disease
severity assessed by using validated score systems (ie, SCORAD; eczema area and severity index
[EASI]; six area, six sign atopic dermatitis [SASSAD]). The pooled analysis of three studies did not
show a difference between montelukast and placebo in improving disease severity (standardized
mean difference 0.29, 95% CI -0.23 to 0.81) and pruritus and in reducing the need for topical
corticosteroids. In the two studies comparing montelukast with conventional treatment,
participants using montelukast experienced improvement in disease severity in one study but no
effect in the other study [162,163]. All trials were of low quality with a significant risk of bias.
Because of the limited and low-quality available evidence, the role of leukotriene receptor
antagonists in the management of atopic dermatitis remains uncertain. While waiting for larger
and well-designed studies, we do not support the use of this class of agents for adults or children
with atopic dermatitis.
REFERRAL
Many patients with atopic dermatitis can initially be treated by a nonspecialist. We suggest that
patients be referred to a specialist (eg, dermatologist, allergist) in the following circumstances:
● When the diagnosis is uncertain
● When patients have failed to respond to appropriate therapy
● If treatment of atopic dermatitis of the face or skin folds with high potency topical
corticosteroids is being contemplated
● If treatment with systemic immunosuppressive agents is being considered
PREGNANCY
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The treatment of atopic dermatitis in pregnant women is discussed separately. (See "Recognition
and management of allergic disease during pregnancy", section on 'Atopic dermatitis'.)
PREVENTION
Skin barrier enhancement — Epidermal barrier dysfunction is recognized as a key factor in the
initiation and progression of atopic dermatitis. Two randomized trials, one performed in Japan and
the other in the United States and United Kingdom found that the enhancement of a defective
skin barrier with daily application of emollients in the first months of life reduce the incidence of
atopic dermatitis in infants at increased risk (ie, those with a parent or sibling with atopic
dermatitis) [164,165].
In the United States and United Kingdom trial, 124 neonates received daily emollients (oil,
cream/gel, or ointment) on the entire body surface. At 24 weeks, the cumulative incidence of
atopic dermatitis was 22 percent in the emollient group versus 43 percent in the control group,
with a relative risk reduction of 49 percent.
In the Japanese study, 118 neonates at increased risk of atopic dermatitis received a daily
application of an emulsion-type emollient from the first week of life or no treatment [165]. At 32
weeks, 19 of 59 infants in the emollient group and 28 of 59 in the control group had developed
atopic dermatitis (32 versus 43 percent, relative risk reduction 26 percent). There were no
differences between the two groups in the levels of IgE against egg white.
Although the long-term efficacy of this treatment needs to be evaluated in larger studies with
extended follow-up, emollient therapy from birth is a simple, inexpensive, and safe intervention
that may prevent the onset of atopic dermatitis in the first year of life. A cost-effectiveness analysis
indicated that daily skin moisturization in the first six months of life is likely a cost-effective
strategy for the prevention of atopic dermatitis; among several emollient products examined in the
study, petrolatum was the most cost-effective [166].
Probiotics and dietary supplements — Probiotic supplementation in pregnant mothers and

infants at risk for atopic dermatitis may prevent the development of the disease in children
younger than three years [167]. A 2014 meta-analysis of 16 randomized trials including
approximately 3500 participants found that probiotics given in the prenatal and postnatal period
reduced the risk of atopic dermatitis in the first years of life in both children at high risk of atopic
dermatitis and in those from the general population (pooled odds ratio [OR] 0.56, 95% CI
0.52-0.60) [168].
25 of 60 24/05/2019, 12:25
However, two subsequent randomized trials did not confirm this finding [169,170]. In one study, a
multispecies probiotic preparation or placebo was given to 454 unselected women at 36 weeks
gestation and their infants to age six months [169]. At two years, the cumulative frequency of
eczema was similar in the probiotic and placebo groups (34 versus 32 percent; OR 1.07, 95% CI
0.7-1.6). In another randomized trial including 184 children at high risk for allergic disease,
probiotic supplementation with Lactobacillus rhamnosus GG during the first six months of life did
not decrease the cumulative incidence of eczema at two years of age, compared with placebo (29
versus 31 percent; hazard ratio [HR] 0.95, 95% CI 0.59-1.53) [170]. The cumulative incidences of
asthma at five years were also not significantly different in the two groups (10 versus 17 percent;
HR 0.88, 95% CI 0.41-1.87). (See "Prebiotics and probiotics for prevention of allergic disease".)
A few small randomized trials have evaluated the role of vitamin D supplementation in the
prevention of winter-related exacerbation of atopic dermatitis [171-173]. In the largest study, 107
children with a history of atopic dermatitis worsening during winter were treated with 1000 IU daily
of vitamin D or placebo for one month [171]. The primary outcome was a reduction in the clinician-
measured eczema area and severity index (EASI). At the end of the study, the mean decrease in
the EASI score was 6.5 in the vitamin D group and 3.3 in the placebo group.
Although the results of these trials suggest that winter supplementation of vitamin D may be
beneficial for patients with atopic dermatitis, larger well-designed studies are needed to clarify the
role of vitamin D in the prevention and treatment of atopic dermatitis.
Nutritional interventions — Previous international guidelines recommended the use of

hydrolyzed formula for the prevention of allergic diseases in high-risk infants who cannot be
exclusively breastfed [174,175]. However, the results of a 2016 systematic review and meta-
analysis of 37 randomized trials evaluating the effect of hydrolyzed formula in infancy on the risk
of childhood eczema, wheezing, allergic rhinitis, or food allergy do not support this
recommendation [176]. This meta-analysis did not find a significant difference between
hydrolyzed formula and standard cow's milk formula in the risk of eczema at age 0 to 4 years (OR
0.84, 95% CI 0.67-1.07) or 5 to 14 years (OR 0.86, 95% CI 0.72-1.02). (See "Introducing formula
to infants at risk for allergic disease".)
SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Atopic dermatitis".)
26 of 60 24/05/2019, 12:25
INFORMATION FOR PATIENTS
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics."
The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading
level, and they answer the four or five key questions a patient might have about a given condition.
These articles are best for patients who want a general overview and who prefer short, easy-to-
read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and
more detailed. These articles are written at the 10th to 12th grade reading level and are best for
patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or
e-mail these topics to your patients. (You can also locate patient education articles on a variety of
subjects by searching on "patient info" and the keyword(s) of interest.)
● Basics topics (see "Patient education: Eczema (atopic dermatitis) (The Basics)" and "Patient
education: Giving your child over-the-counter medicines (The Basics)" and "Patient
education: Topical corticosteroid medicines (The Basics)")
● Beyond the Basics topics (see "Patient education: Eczema (atopic dermatitis) (Beyond the
Basics)")
SUMMARY AND RECOMMENDATIONS
● The goals of treatment for atopic dermatitis are to reduce symptoms (pruritus and dermatitis),
prevent exacerbations, and minimize therapeutic risks. (See 'Introduction' above.)
● The optimal management requires a multipronged approach that involves the elimination of
exacerbating factors, restoration of the skin barrier function and hydration of the skin, patient
education, and pharmacologic treatment of skin inflammation (algorithm 1). (See 'General
approach' above.)
● We suggest that patients with mild to moderate atopic dermatitis be initially treated with
topical corticosteroids and emollients (Grade 2B). The choice of the corticosteroid potency
should be based upon the patient's age, body area involved, and degree of skin
inflammation.
• For patients with mild atopic dermatitis, we suggest a low potency (groups five and six
(table 1)) corticosteroid cream or ointment (eg, desonide 0.05%, hydrocortisone 2.5%).
27 of 60 24/05/2019, 12:25
Topical corticosteroids can be applied once or twice daily for two to four weeks.
• For patients with moderate disease, we suggest medium to high potency (groups three
and four (table 1)) corticosteroids (eg, fluocinolone 0.025%, triamcinolone 0.1%,
betamethasone dipropionate 0.05%). (See 'Topical corticosteroids' above.)
• The face and skin folds are areas that are at high risk for atrophy with corticosteroids.
Initial therapy in these areas should start with a low potency corticosteroid (group VI
(table 1)), such as desonide 0.05% ointment for up to three weeks. (See 'Topical
corticosteroids' above.)
● We suggest that patients with atopic dermatitis involving the face or skin folds that is not
controlled with topical corticosteroids, be treated with a topical calcineurin inhibitor (ie,
tacrolimus or pimecrolimus) (Grade 2B). (See 'Topical calcineurin inhibitors' above.)
● We suggest proactive therapy to prevent relapse in adolescents and adults with moderate to
severe (picture 1A-B) atopic dermatitis that responds to continuous therapy with topical
corticosteroids or calcineurin inhibitors (Grade 2A). We suggest medium to high potency
topical corticosteroids (groups three to five) (table 1) rather than topical calcineurin inhibitors
for proactive intermittent therapy (Grade 2B). Topical corticosteroids are applied once daily
for two consecutive days per week for up to 16 weeks. (See 'Maintenance and prevention of
relapses' above.)
● Patients with moderate to severe atopic dermatitis that is not controlled with optimal topical
therapy may require phototherapy or systemic immunosuppressant treatment to achieve
adequate disease control (algorithm 1). These treatments are not suitable for infants and
young children. In older children and adolescents, they should be used when other
management options have failed and the disease has a significant impact on the quality of
life. (See 'Patients with moderate to severe disease' above.)
Use of UpToDate is subject to the Subscription and License Agreement.
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Topic 1730 Version 74.0
43 of 60 24/05/2019, 12:25
GRAPHICS
Management of atopic dermatitis
44 of 60 24/05/2019, 12:25
For examples of low-, medium-, and high-potency topical corticosteroids, please refer to the UpToDate table on
topical corticosteroids.
TCS: topical corticosteroid; TCI: topical calcineurin inhibitor.

* Trigger/exacerbating factors:
Irritants (soaps, detergents)
Skin infections (Staphylococcus aureus, herpes simplex)
Contact, inhalant, or food allergens
¶ Mild atopic dermatitis – Areas of dry skin, infrequent itching (with or without small areas of redness); little impact on
everyday activities, sleep, and psychosocial wellbeing.
Δ Moderate atopic dermatitis – Areas of dry skin, frequent itching, redness (with or without excoriation and localized skin
thickening); moderate impact on everyday activities and psychosocial wellbeing, frequently disturbed sleep.
◊ Severe atopic dermatitis – Widespread areas of dry skin, incessant itching, redness (with or without excoriation,
extensive skin thickening, bleeding, oozing, cracking, and alteration of pigmentation); severe limitation of everyday
activities and psychosocial functioning, nightly loss of sleep.
§ Crisaborole is approved for mild to moderate atopic dermatitis in adults and children >2 years.
¥ TCIs are approved for mild to moderate atopic dermatitis in adults and children >2 years. TCIs include tacrolimus and
pimecrolimus.
‡ Dupilumab is approved for moderate to severe atopic dermatitis in adults whose disease is not adequately controlled
with topical prescription therapies.
Graphic 115549 Version 1.0
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Comparison of representative topical corticosteroid preparations (classified

according to the US system)
Available
strength(s),
Vehicle Trade names
Potency group* Corticosteroid percent
type/form (United States)
(except as
noted)
Super-high potency Betamethasone Ointment, optimized Diprolene 0.05

(group 1) dipropionate,
Lotion Diprolene 0.05
augmented
Gel Diprolene 0.05
Clobetasol Ointment Temovate 0.05

propionate
Cream Temovate 0.05
Cream, emollient Temovate E 0.05

base
Gel Temovate 0.05
Lotion Clobex 0.05
Foam aerosol Olux-E 0.05
Foam aerosol (scalp) Olux 0.05
Shampoo Clobex 0.05
Solution (scalp) Temovate, Cormax 0.05
Spray aerosol Clobex 0.05
Diflucortolone Ointment, oily cream Nerisone Forte 0.3

valerate (not (United Kingdom,
available in United others)
States)
Fluocinonide Cream Vanos 0.1
Flurandrenolide Tape (roll) Cordran 4 mcg/cm 2
Halobetasol Ointment Ultravate 0.05

propionate
Cream Ultravate 0.05
Lotion Ultravate 0.05
High potency Amcinonide Ointment Cyclocort ¶ , Amcort ¶ 0.1

(group 2)
Betamethasone Ointment Diprosone 0.05
dipropionate
Cream, augmented Diprolene AF 0.05
formulation (AF)
Clobetasol Cream Impoyz 0.025

propionate
Desoximetasone Ointment Topicort 0.25
Cream Topicort 0.25
Spray Topicort 0.25
Gel Topicort 0.05
Diflorasone Ointment ApexiCon ¶ , Florone ¶ 0.05

diacetate
Cream, emollient ApexiCon E 0.05
Fluocinonide Ointment Lidex ¶ 0.05
46 of 60 24/05/2019, 12:25
Gel Lidex ¶ 0.05
Cream anhydrous Lidex ¶ 0.05
Solution Lidex ¶ 0.05
Halcinonide Ointment Halog 0.1
Cream Halog 0.1
Halobetasol Lotion Bryhali 0.01

propionate
High potency Amcinonide Cream Cyclocort ¶ , Amcort ¶ 0.1

(group 3)
Lotion Amcort ¶ 0.1
Betamethasone Cream, hydrophilic Diprosone 0.05

dipropionate emollient
Betamethasone Ointment Valisone ¶ 0.1

valerate
Foam Luxiq 0.12
Desoximetasone Cream Topicort LP 0.05
Diflorasone Cream Florone ¶ 0.05

diacetate
Diflucortolone Cream, oily cream, Nerisone (Canada, 0.1

valerate (not ointment United Kingdom,
available in United others)
States)
Fluocinonide Cream aqueous Lidex-E ¶ 0.05

emollient
Fluticasone Ointment Cutivate 0.005

propionate
Mometasone furoate Ointment Elocon 0.1
Triamcinolone Ointment Kenalog ¶ 0.5

acetonide
Cream Triderm, Aristocort 0.5
HP ¶
Medium potency Betamethasone Spray Sernivo 0.05

(group 4) dipropionate
Clocortolone pivalate Cream Cloderm 0.1
Fluocinolone Ointment Synalar ¶ 0.025

acetonide
Flurandrenolide Ointment Cordran 0.05
Hydrocortisone Ointment Westcort 0.2

valerate
Mometasone furoate Cream Elocon 0.1
Lotion Elocon 0.1
Solution Elocon ¶ 0.1
Triamcinolone Cream Kenalog ¶ 0.1

acetonide
Ointment Kenalog ¶ 0.1
Aerosol spray Kenalog 0.2 mg per 2 second

spray
Lower-mid potency Betamethasone Lotion Diprosone 0.05

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Betamethasone Cream Beta-Val, Valisone ¶ 0.1

valerate
Desonide Ointment DesOwen, 0.05

Tridesilon ¶
Gel Desonate 0.05
Fluocinolone Cream Synalar ¶ 0.025

acetonide
Flurandrenolide Cream Cordran 0.05
Lotion Cordran 0.05
Fluticasone Cream Cutivate 0.05

propionate
Lotion Cutivate 0.05
Hydrocortisone Ointment Locoid 0.1

butyrate
Cream Locoid, Locoid 0.1
Lipocream
Lotion, spray Cortizone 10 0.1

maximum
Lotion Locoid 0.1
Solution Locoid 0.1
Hydrocortisone Cream Pandel 0.1

probutate
Hydrocortisone Cream Westcort ¶ 0.2

valerate
Prednicarbate Cream, emollient Dermatop 0.1
Ointment Dermatop 0.1
Triamcinolone Lotion Kenalog ¶ 0.1

acetonide
Ointment Kenalog ¶ 0.025
Low potency Alclometasone Ointment Aclovate 0.05

Cream Aclovate 0.05
Betamethasone Lotion Beta-Val, Valisone ¶ 0.1

valerate
Desonide Cream DesOwen, 0.05

Tridesilon ¶
Lotion DesOwen, LoKara 0.05
Foam Verdeso 0.05
Fluocinolone Cream Synalar ¶ 0.01

acetonide
Solution Synalar ¶ 0.01
Shampoo Capex 0.01
Oil (scalp) Δ Derma-Smoothe/FS 0.01

Scalp
Oil (body) Δ Derma-Smoothe/FS 0.01

Body
Triamcinolone Cream Kenalog ¶ , 0.025

acetonide Aristocort ¶
Lotion Kenalog ¶ 0.025
48 of 60 24/05/2019, 12:25
Least potent Hydrocortisone Ointment Hytone 2.5

(group 7) (base, ≥2%)
Cream Hytone, Nutracort ¶ 2.5
Lotion Hytone, Ala Scalp, 2.5 or 2

Scalacort
Solution Texacort 2.5
Hydrocortisone Ointment Cortaid, Hytone, 1

(base, <2%) Nutracort
Cream Cortaid, Hytone, 1

Synacort
Lotion Aquanil HC, Sarnol- 1

HC, Cortizone 10
Spray Cortaid 1
Solution Cortaid, Noble, Scalp 1

relief
Ointment Cortaid 0.5
Cream Cortaid 0.5
Hydrocortisone Ointment Pramosone 1 or 2.5

acetate with
Cream Pramosone, 1 or 2.5
pramoxine 1%
Analpram-HC
combination
Lotion Pramosone, 1 or 2.5
Analpram-HC
Aerosol foam Epifoam 1
US: United States.

* Listed by potency according to the US classification system: group 1 is the most potent, group 7 is the least potent.
Other countries use a different classification system with only four or five groups.
¶ Inactive United States trade name for specific product; brand may be available outside United States.
Δ 48% refined peanut oil.
Data from:
1. Lexicomp Online. Copyright © 1978-2019 Lexicomp, Inc. All Rights Reserved.
2. Tadicherla S, Ross K, Shenefelt D. Topical corticosteroids in dermatology. Journal of Drugs in Dermatology 2009;
12:1093.
3. U.S. Food & Drug Administration Approved Drug Products with Therapeutic Equivalence (Orange Book). Available
at: https://www.accessdata.fda.gov/scripts/cder/ob/default.cfm (Accessed on June 18, 2017).
49 of 60 24/05/2019, 12:25
Adult atopic dermatitis
Chronic atopic dermatitis with lichenification (skin thickening and enhancement of skin
markings) of the knee flexures in a 22-year-old woman.
Copyright © Monica Standish, RN, Dermatlas; http://www.dermatlas.org.
50 of 60 24/05/2019, 12:25
Adult chronic atopic dermatitis
Lichenified, hyperpigmented plaque in the elbow flexure of a 35-year-old woman with

atopic dermatitis.
Copyright © Yusoff Saifuzzaman, MD, Dermatlas; http://www.dermatlas.org.
51 of 60 24/05/2019, 12:25
Atopic dermatitis: Infantile
Confluent erythema, microvesiculation, scaling, and crusting on the face, with

similar involvement (to a lesser degree) on the trunk and arms.
Reproduced with permission from: Fitzpatrick TB, Johnson RA, Wolff K, et al (Eds).
Color Atlas and Synopsis of Clinical Dermatology, 3rd ed, McGraw-Hill, New York,
1997. Copyright © McGraw-Hill.
52 of 60 24/05/2019, 12:25
Atopic dermatitis on the backs of the knees
Atopic dermatitis often affects the crease of the skin where the leg bends.
Courtesy of James C Shaw, MD.
53 of 60 24/05/2019, 12:25
Staphylococcus aureus infection in atopic dermatitis
Pustules and honey-colored crusting are seen on the dorsal hand of this patient
with infected atopic dermatitis.
Courtesy of Joseph Morelli, MD.
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Staphylococcus aureus infection in atopic dermatitis
Honey-colored crusts are seen on the postauricular skin of this patient with
infected atopic dermatitis.
Courtesy of Joseph Morelli, MD.
55 of 60 24/05/2019, 12:25
Eczema herpeticum
Punched-out ulcers are due to herpes simplex virus infection present on the arm
of this patient with underlying atopic dermatitis.
Reproduced with permission from: Fleisher GR, Ludwig S, Baskin MN. Atlas of
Pediatric Emergency Medicine, Lippincott Williams & Wilkins, Philadelphia 2004.
Copyright ©2004 Lippincott Williams & Wilkins.
56 of 60 24/05/2019, 12:25
Eczema herpeticum
Hemorrhagic crusts and vesicles due to herpes simplex virus infection are
present on the hand of this infant with underlying atopic dermatitis.
Copyright © 2004 Lippincott Williams & Wilkins.
57 of 60 24/05/2019, 12:25
Eczema herpeticum
Hemorrhagic crusts and vesicles due to herpes simplex virus infection are
present on the face of this infant with underlying atopic dermatitis.
Copyright © 2004 Lippincott Williams & Wilkins.
58 of 60 24/05/2019, 12:25
Molluscum contagiosum in a patient with atopic

dermatitis
Lesions are present on a background of atopic dermatitis of the flexural creases.
Reproduced with permission from: Goodheart HP. Goodheart's Photoguide of

Common Skin Disorders, 2nd ed, Lippincott Williams & Wilkins 2003. Copyright ©
2003 Lippincott Williams & Wilkins.
59 of 60 24/05/2019, 12:25
Contributor Disclosures
William L Weston, MD Nothing to disclose William How e, MD Nothing to disclose Robert P Dellavalle,
MD, PhD, MSPH Grant/Research/Clinical Trial Support: Pfizer Pharmaceuticals [Independent research grant
to the University of Colorado (Development of patient decision aids)]. Consultant/Advisory Boards: Altus Labs
[Burn, itch (Cannabidiol, palmitoylethanolamide)]. Equity Ownership/Stock Options: Altus Labs [Burn, itch
(Cannabidiol, palmitoylethanolamide)]. Other Financial Interest: Editorial stipends from the Journal of
Investigative Dermatology and the Journal of the American Academy of Dermatology. Moise L Levy,
MD Grant/Research/Clinical Trial Support: Amicus Therapeutics [Epidermolysis bullosa (Novel topical
therapy)]; Janssen Pharmaceutica [Psoriasis (Guselkumab)]; Pfizer [Atopic dermatitis (Janus kinase inhibitor)].
Consultant/Advisory Boards: Pfizer; Regeneron Pharmaceuticals [Atopic dermatitis (Janus kinase inhibitor,
dupilumab)]. Patent Holder: Incontinentia pigmenti (NEMO gene mutations). Other Financial Interest: Castle
Creek Pharmaceuticals [Epidermolysis bullosa (Diacerein ointment)]. Joseph Fow ler, MD Grant/Research
/Clinical Trial Support: Merck; Pfizer; Novartis; Eli Lilly and Company; Regeneron; Asana BioSciences
[Eczema, psoriasis (Crisaborole, MK3223, tofacitinib, secukinumab, ixekizumab, dual Janus kinase/spleen
tyrosine kinase inhibitor)]. Speaker's Bureau: SmartPractice [Allergic contact dermatitis (Epicutaneous patch
test)]. Rosamaria Corona, MD, DSc Nothing to disclose
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must conform
to UpToDate standards of evidence.
Conflict of interest policy
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Treatment of atopic dermatitis (eczema) - UpToDate https://www.uptodate.com/contents/treatment-of-atopic-dermatitis-eczema...

Official reprint from UpToDate®

Wolters Kluwer Health

Treatment of atopic dermatitis (eczema)

● (See "Management of severe atopic dermatitis (eczema) in children".)

Elimination of exacerbating factors — Exacerbating factors in atopic dermatitis that disrupt an

● Avoid trigger factors such as heat, low humidity

● Treat stress and anxiety

Aeroallergens and food allergens — There is controversy regarding whether environmental

Hypersensitivity to house dust mites (eg, Dermatophagoides pteronyssinus, D. farinae), animal

Maintaining skin hydration

Emollients and moisturizers — Skin hydration is a key component of the overall

● Four studies examined oat-containing moisturizers versus no treatment or control. No

Controlling pruritus — Oral H1 antihistamines are widely used as a therapeutic adjunct in

The efficacy of second-generation, less sedating, H1 antihistamines, such as fexofenadine,

Patient education — Patient education is an important component of the management of atopic

PATIENTS WITH MILD TO MODERATE DISEASE

Maintenance therapy that includes intermittent use of a topical corticosteroid or a topical

Efficacy and adverse effects — A systematic review of randomized trials identified 83

telangiectasias, folliculitis, and contact dermatitis. (See "General principles of dermatologic

Topical calcineurin inhibitors — Topical calcineurin inhibitors are nonsteroidal

● A subsequent meta-analysis of four randomized trials comparing tacrolimus with

● In a systematic review of 31 randomized trials, pimecrolimus was significantly better than

Issues of concern include:

inhibitors [65,66]. The Pediatric Eczema Elective Registry (PEER) is an industry-sponsored,

● Use these agents only as second-line therapy in patients unresponsive to or intolerant of

Crisaborole — Crisaborole is a boron-based, small-molecule, topical phosphodiesterase 4

Maintenance and prevention of relapses — We suggest proactive therapy to prevent relapse in

In meta-analyses of randomized trials, proactive, intermittent therapy with moderate to high

adverse effects with corticosteroids, as illustrated below:

Treatment of acute exacerbations — In adolescents and adults, an acute exacerbation of

PATIENTS WITH MODERATE TO SEVERE DISEASE

continued as needed during phototherapy. Additional emollients may be necessary since

Side effects of cyclosporine include nephrotoxicity, hypertension, hypertrichosis, gum hyperplasia,

Other systemic immunosuppressants — Second-line systemic immunosuppressive agents for

PATIENTS WITH SEVERE REFRACTORY DISEASE

Staphylococcus aureus — S. aureus is a frequent skin colonizer in patients with atopic

unusual organisms [108].

Anti-IL-31 antibodies — Nemolizumab is a humanized monoclonal antibody against the receptor

Anti-IL-13 antibodies — Lebrikizumab is a monoclonal antibody that binds specifically to soluble

Complementary and alternative therapies

● Similar results were provided by another randomized trial including 70 children of 6 to 12

Leukotriene receptor antagonists — Montelukast, an oral leukotriene receptor antagonist

● When the diagnosis is uncertain

● When patients have failed to respond to appropriate therapy

● If treatment with systemic immunosuppressive agents is being considered

Probiotics and dietary supplements — Probiotic supplementation in pregnant mothers and

Nutritional interventions — Previous international guidelines recommended the use of

SOCIETY GUIDELINE LINKS

INFORMATION FOR PATIENTS

SUMMARY AND RECOMMENDATIONS

Use of UpToDate is subject to the Subscription and License Agreement.

1. Weidinger S, Novak N. Atopic dermatitis. Lancet 2016; 387:1109.

4. Tollefson MM, Bruckner AL, Section On Dermatology. Atopic dermatitis: skin-directed

7. Ellis C, Luger T, Abeck D, et al. International Consensus Conference on Atopic Dermatitis II

14. Lever R, MacDonald C, Waugh P, Aitchison T. Randomised controlled trial of advice on an

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