Access to this full-text is provided by Wiley.
Content available from JEADV Clinical Practice
This content is subject to copyright. Terms and conditions apply.
JEADV Clinical Practice
ORIGINAL ARTICLE
Management of Mild‐to‐Moderate Atopic Dermatitis
With Topical Treatments by Dermatologists:
A Questionnaire‐Based Study
Lawrence F. Eichenfield
1
| Linda F. Stein Gold
2
| Adelaide A. Hebert
3
| Lyn Guenther
4
| Yuliya Valdman‐Grinshpoun
5,6
|
Dan Ben‐Amitai
7
| Roni P. Dodiuk‐Gad
8,9,10
| Michael J. Cork
11,12
| Valeria Aoki
13
| Chia‐Yu Chu
14
|
Jianzhong Zhang
15
| Lin Ma
16
| Hidehisa Saeki
17
| Paula C. Luna
18
| Mark Jean‐Aan Koh
19
1
Departments of Dermatology and Pediatrics, University of California San Diego and Rady Children's Hospital‐San Diego, San Diego, California,
USA |
2
Henry Ford Health System, Detroit, Michigan, USA |
3
UTHealth McGovern Medical School, Houston, Texas, USA |
4
Department of Dermatology,
Western University, London, Ontario, Canada |
5
Department of Dermatology, Soroka University Medical Center, Beer Sheva, Israel |
6
Faculty of Health
Sciences, Ben‐Gurion University of the Negev, Beer Sheva, Israel |
7
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel |
8
Department of
Dermatology, University of Toronto, Toronto, Ontario, Canada |
9
Department of Dermatology, Emek Medical Center, Afula, Israel |
10
Department of
Medicine, Ruth and Bruce Rappaport Faculty of Medicine, Technion Institute of Technology, Haifa, Israel |
11
Sheffield Dermatology Research and
Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK |
12
Sheffield Children's Hospital, Sheffield,
UK |
13
Department of Dermatology, University of São Paulo School of Medicine, São Paulo, Brazil |
14
Department of Dermatology, National Taiwan
University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan |
15
Department of Dermatology, Peking University People's Hospital,
Beijing, China |
16
Department of Dermatology, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University, Beijing,
China |
17
Department of Dermatology, Nippon Medical School, Tokyo, Japan |
18
Department of Dermatology, Hospital Alemán, Buenos Aires,
Argentina |
19
Department of Dermatology, KK Women's and Children's Hospital, Singapore, Singapore
Correspondence: Lawrence F. Eichenfield (leichenfield@rchsd.org)
Received: 25 July 2024 | Revised: 27 November 2024 | Accepted: 17 December 2024
Funding: This study was sponsored by Pfizer Inc., New York, NY, USA.
Keywords: atopic dermatitis | dermatologic therapy | eczema
ABSTRACT
Needs edits as it misses the important point of specifying the non‐corticosteroids and should not be in the past tense. “Atopic
dermatitis (AD) is a skin disease that causes red, dry skin patches that may itch intensely, and may be persistent or intemittent.
Most patients with mild‐to‐moderate AD use topical corticosteroids or topical non‐steroids to help them get better. This study
looked at how dermatologists treat AD in different parts of the world. Dermatologists in North America, the Middle East, Asia,
South America and the UK were asked questions about how they treat AD with topical medications. Most dermatologists use a
type of cream or ointment called topical corticosteroids (TCSs) as the first treatment for ≤4 weeks. Weaker TCSs are used for
younger patients and sensitive parts of the body. After using TCSs for a few weeks, patients visit their dermatologist to check if
the treatment is working. Dermatologists advise patients to continue with the same TCS, use less of the TCS or change to non‐
steroid topical creams or ointments such as calcineurin inhibitors, crisaborole or topical JAK inhibitors. Sometimes treatments
are changed if the patient's skin becomes infected, reacts badly to the medication or there are concerns about side effects.
Patients also change treatment if their AD worsens. Sometimes it is difficult for patients to access treatments where they live.
This study gives important information about how dermatologists treat mild‐to‐moderate AD. Treatment depends on factors
like the patient's age, how severe the disease is, and if the patient is worried about using some creams and ointments. This
information should help dermatologists plan the best treatment for patients with AD.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly
cited.
© 2025 The Author(s). JEADV Clinical Practice published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.
1of11JEADV Clinical Practice, 2025; 1–11
https://doi.org/10.1002/jvc2.611
1 | Introduction
Atopic dermatitis (AD) is a chronic, immune‐mediated,
inflammatory skin disease with a relapsing‐remitting course
[1]. Characterized by poorly demarcated eczematous lesions,
pruritus and skin pain that is frequently accompanied by mul-
tiple comorbidities, AD has a negative impact on patient and
caregiver quality of life [2–4].
The initial treatment of AD requires basic management with
good skin care (including the use of moisturizers and warm
baths with gentle non‐soap cleansers) and the avoidance of
triggers [5–11]. When the use of emollients and other good
skin care practices fail to maintain disease control, a topical
anti‐inflammatory is often prescribed [5–11]. Topical corti-
costeroids (TCSs) are the mainstay topical anti‐
inflammatory treatment according to current guidelines
[5–11]. However, topical calcineurin inhibitors (TCIs)
[6–11] and phosphodiesterase 4 (PDE4) inhibitors (e.g.,
crisaborole) are alternatives [5, 6, 12, 13]. Although not
included in some current guidelines, topical Janus kinase
inhibitors (JAKis) (e.g., ruxolitinib and delgocitinib) are
considered an emerging treatment option for AD [8, 10, 12].
Ruxolitinib, 1.5%, cream is included in the recent American
Academy of Dermatology guideline as a treatment option for
short‐term and noncontinuous chronic treatment of mild‐to‐
moderate AD in patients ≥12 years [6]. Traditionally, a
reactive or ‘use when necessary’approach has been used to
treat AD, with topical anti‐inflammatory therapies being
reintroduced to treat active eczema and flares. However,
guidance documents currently advise a more proactive
approach for patients having recurrent flares. Proactive
treatment consists of long‐term intermittent application of
topical anti‐inflammatory agents to previously and newly
affected areas as maintenance together with good skin care
to achieve longer‐lasting disease control and a reduction in
the incidence of flares [5–7, 14].
Clinical guidelines provide general recommendations which
areconsideredbestpracticeinthetreatmentandmanage-
ment of mild‐to‐moderate AD; however, a more individual-
ized approach is often required [15]. The regimen selected is
often dependent on patient‐specific factors such as age, dis-
ease severity, location of involvement, previous adverse ef-
fects, response to therapy and the frequency and severity of
flares [6–11, 16–18]. Moreover, treatment regimens are often
based on regional drug availability, cost, patient education
and the training, speciality and clinical experience of the
healthcare provider [16–18].
To assess the management of mild‐to‐moderate AD with topical
therapies across various geographic regions, an expert panel of
dermatologists was selected to provide insight into their clinical
practice.
2 | Methods
2.1 | Study Design
Dermatologists from multiple global regions were invited to
participate in the study. Those who accepted the invitation
were sent an electronic questionnaire consisting of 43 ques-
tions, of which 21 were open‐ended and 22 were closed‐ended
(Appendix S1). Participants were asked to share their knowl-
edge and experience in the management of mild‐to‐moderate
AD based on patient age (< 2, 2–12 and > 12 years) and disease
severity (mild and moderate AD). The questionnaire was
completed by all participants by November 2022. Question-
naire responses were anonymous and were transferred to
Microsoft Excel for analysis. This study was conducted in
compliance with the ethical principles originating in, or
derived from, the Declaration of Helsinki and is in compliance
with all International Conference on Harmonisation Good
Clinical Practice Guidelines.
2.2 | Participants' Roles
Participants were all board‐certified dermatologists selected
based on their knowledge and expertise in the management of
AD. In addition, participants had to be widely recognized
within their field of practice in their respective countries. Par-
ticipants provided insight into the management of mild‐to‐
moderate AD with topical treatments based on their clinical
practice by providing answers to a questionnaire.
Summary
•Atopic dermatitis (AD) is a skin disease that causes red,
dry skin patches that may itch intensely, and can affect
people for a long time. Most patients with mild‐to‐
moderate AD use special creams and ointments to help
them get better. This study looked at how dermatologists
treat AD in different parts of the world. Dermatologists
in North America, the Middle East, Asia, South America
and the UK were asked questions about how they treat
AD with creams and ointments.
•In this study, most dermatologists used a type of cream
or ointment called topical corticosteroids (TCSs) as the
first treatment for ≤4 weeks. Weaker TCSs were used
for younger patients and sensitive parts of the body.
After using TCSs for a few weeks, patients visited their
dermatologist to check if the treatment was working.
Dermatologists advised patients to continue with the
same TCS, use less of the TCS or change to a different
type of cream or ointment.
•Sometimes patients had to change treatment if their skin
became infected or reacted badly to TCSs. Patients also
changed treatment if their AD got worse or if they were
afraid to use stronger creams and ointments. Sometimes
it was difficult for patients to access treatments where
they lived.
•This study gives important information about how der-
matologists treat mild‐to‐moderate AD. Treatment
depends on factors like the patient's age, how severe the
disease is, and if the patient is worried about using some
creams and ointments. This information should help
dermatologists plan the best treatment for patients
with AD.
2of11 JEADV Clinical Practice, 2025
2.3 | Nomenclature Relating to Topical
Treatments
TCSs were classified according to the United States–based
classification system comprising several groups of TCSs: high‐
potency (super‐high potency [class I] and high potency [class II]
TCSs), medium‐potency (medium‐to‐high [class III] and
medium potency [class IV and V] TCSs) and low‐potency (low‐
[class VI] and least‐potency [class VII]) [19]. TCIs, PDE4
inhibitors and JAKis are referred to as non‐TCS treatments.
2.4 | Statistical Analysis
All information collected from the questionnaire was presented
descriptively, with no formal statistical analysis performed. The
answers to close‐ended questions were summarized and re-
ported, and the open‐ended questions were reported according
to trends. For some questions, not all participants provided a
response.
3 | Results
3.1 | Participants
An expert panel of 17 dermatologists from North America
(n= 5), the Middle East (n= 4), Asia (n= 5), South America
(n= 2) and the UK (n= 1) participated. The majority (16 of 17)
of participants reported that TCIs were approved for use in
their region for use in patients aged > 2 years, while almost half
(8 of 17) reported TCIs were not approved for use in patients
< 2 years of age. Most participants reported that crisaborole was
approved within their region of practice; 4 of 17 and 2 of 17
participants reported that crisaborole was not approved for use
in patients < 2 years and patients > 2 years, respectively.
3.2 | Differentiation of Mild and Moderate AD
Most participants (14 of 16) indicated that they consider
multiple factors when differentiating between mild and
moderate AD. Some participants noted that compared to mild
AD, moderate AD typically involves a larger body surface area,
more severe pruritus or more extensive AD‐related lesions,
lichenification and excoriations, often requiring more potent
topical treatment options to maintain control. Only 2 of 16
participants regularly use scoring systems in daily practice to
determine the severity of disease.
3.3 | Daily Skin Care Regimens
Most participants (15 of 16) recommend daily skin care to
their patients including the use of a moisturizer (12 of 16),
amildsoapcleanserorgentlenon‐soap cleanser (9 of 16)
and daily short baths or showers (9 of 16) and warm water
baths (2 of 16) as part of their preferred daily skin care
regimen.
3.4 | First‐Line Pharmacologic Treatments for
Initial Control
Nearly all participants indicated that they would use TCS as
first‐line treatment regardless of age. For a child aged < 2 years,
9 of 17 participants would select a low‐to‐medium–potency
TCS, while higher‐potency TCS were preferred for patients aged
2–12 and > 12 years (Figure 1). In addition, participants indi-
cated that they would prescribe a TCS of a higher potency for
patients with moderate AD versus mild AD (Figure 2).
The potency of TCS selected was dependent on patient age,
disease severity and regions of the body affected. None of the
participants selected TCIs, topical crisaborole or topical JAKis
(non‐TCS) as their preferred first‐line topical treatment irre-
spective of age or disease severity; however, participants who
selected ‘other’in the questionnaire stated that they would
prescribe either a TCS or a non‐TCS depending on the patient
case (Figures 1and 2).
3.4.1 | Treatment Based on Body Region
All participants (16 of 16) indicated that their choice of top-
ical treatment would depend on the body region being trea-
ted; lower‐potency TCSs and/or non‐TCSs for sensitive
regions (e.g., face, groin and skin folds) and higher‐potency
TCSs for other body regions. For patients aged < 2 years, half
of the participants (8 of 16) indicated that they would pre-
scribe low‐potency TCSs, while several other participants
would prescribe a non‐TCS as monotherapy as an alternative
treatment option to a lower‐potency TCS. The prescribing
patterns for patients aged 2–12 and > 12 years were similar;
however, more participants would prescribe non‐TCSs as
monotherapy as an alternative to a lower‐potency TCS for
mild‐to‐moderate AD in older patient groups. A non‐TCS
would be more likely prescribed among patients with mod-
erate AD versus mild AD.
3.4.2 | Length of Initial Treatment
Most participants would prescribe treatment for < 2 or
≤4 weeks across all age groups and disease severity for
initial control (Figures 3and 4). The length of treatment
selected was not specific to a particular topical treatment
option. Some participants who selected ‘other’indicated
that the length of treatment would be dependent on the
severity of disease.
3.4.3 | Time Until Re‐Evaluation of Treatment
Most participants (11 of 16) indicated that the time until re‐
evaluation of treatment was guided by disease severity assessed
during the initial consultation and subsequent follow‐up visits.
The greater the disease severity, the shorter the time until re‐
evaluation; for more severe cases, participants would advise
periods of 1 to ≤4 weeks until re‐evaluation, and for less severe
cases, they recommended periods of 1–4 months.
3of11
FIGURE 1 | First‐line pharmacologic treatment(s) for initial control of AD in patients aged < 2, 2–12 and > 12 years with mild‐to‐moderate AD.
a
In the questionnaire, this option was only provided for patients aged < 2 years.
b
In the questionnaire, this option was only provided for patients aged
2–12 and > 12 years.
c
In the questionnaire, this option was only provided for patients aged > 12 years. JAKi, Janus kinase inhibitor; TCI, topical
calcineurin inhibitor; TCS, topical corticosteroid.
FIGURE 2 | First‐line pharmacologic treatment(s) for initial control of AD in patients with mild and moderate AD. JAKi, Janus kinase inhibitor;
TCI, topical calcineurin inhibitor; TCS, topical corticosteroid.
4of11 JEADV Clinical Practice, 2025
3.5 | Recommendations for Maintenance
Treatment
After initial treatment, most participants indicated they would
continue the regimen previously prescribed with a scheduled
follow‐up or switch to a non‐TCS (Figures 5and 6).
When asked whether participants generally reduced the dose or
switched to a different treatment option for maintenance
treatment, most participants reported that their choice was
dependent on the patient's case, regardless of the patient's age
or disease severity.
When asked to describe their approach to maintenance
treatment, most participants indicated that their approach
was dependent on the patient case; however, some partici-
pants favoured a proactive approach (i.e., long‐term inter-
mittent application of topical anti‐inflammatory therapies
FIGURE 3 | Length of treatment for initial control of AD in patients aged < 2, 2–12 and > 12 years with mild‐to‐moderate AD. AD, atopic
dermatitis.
FIGURE 4 | Length of treatment for initial control of AD in patients with mild and moderate AD. AD, atopic dermatitis.
5of11
FIGURE 5 | Recommendation for maintenance treatment of AD in patients aged < 2, 2–12 and > 12 years with mild‐to‐moderate AD.
a
Parti-
cipants indicated that depending on the patient case they would either reduce the dose or switch to a non‐TCS.
b
Participants indicated that depending
on the frequency of the flares they would consider the use of a topical anti‐inflammatory as maintenance. AD, atopic dermatitis; TCS, topical
corticosteroid.
FIGURE 6 | Recommendation for maintenance treatment of AD in patients with mild and moderate AD.
a
Participants indicated that
depending on the patient's case, they would either reduce the dose or switch to a non‐TCS.
b
Participants indicated that depending on the
frequency of the flares, they would consider the use of a topical anti‐inflammatory as maintenance. AD, atopic dermatitis; TCS, topical
corticosteroids.
6of11 JEADV Clinical Practice, 2025
as maintenance). Few participants favoured a reactive
approach.
During follow‐up, participants indicated they would prescribe a
non‐TCS plus a TCS across all age groups (16 of 16) depending
on the patient case and disease severity (15 of 16 for mild AD
and 16 of 17 for moderate AD).
3.6 | Treatment of Flares
All participants indicated that they would utilize TCSs for the
treatment of flares, with or without a non‐TCS (often dependent
on patient age, the body region/s affected and/or the overall
disease severity). Medium‐or high‐potency TCSs were more
often prescribed for flares versus low‐potency TCSs, except
when treating more sensitive areas of the skin. Overall, periods
of treatment between 1 and 2 weeks were preferred; however,
longer periods of up to 6 weeks were indicated in the absence of
flare resolution.
3.7 | Deviation From Standard Treatment
Infection was the most common reason for deviating from
standard treatment. Other reasons included misconceptions and
fears regarding the use of corticosteroids (corticophobia), lack of
improvement in disease severity and worsening of AD. In
addition, all participants considered the patient or caregiver's
opinion or preference when determining treatment choice.
3.8 | Limitations and Safety Considerations for
Topical Treatment Options
Several participants listed more than one safety concern and/
or limitation for each topical treatment option. The main
limitations of TCS were adverse effects associated with its use
and corticophobia. The most common adverse effect listed was
skin atrophy. Limitations associated with the use of TCIs
included adverse effects and cost. A burning sensation was the
most common adverse effect of concern. The boxed warning
associated with TCI use in some countries was also a safety
consideration. The most common safety concern for PDE4
inhibitors was application site pain. Cost or lack of coverage of
PDE4 inhibitors by insurance and lack of experience with this
drug class also limited use. Half of the participants (8 of 16)
had no experience with JAKis (two participants indicated that
JAKis were not available within their region). Some partici-
pants listed the cost and/or a lack of coverage by insurance of
JAKis as a limitation and others indicated that the cardio-
vascular or thrombotic events seen with systemic JAKis were a
potential concern.
When asked how application site reactions might be managed
or avoided, answers included patient education and prescribing
TCSs to calm or heal skin followed by non‐TCSs. Other methods
included refrigeration of the topical agent and/or moisturizer or
the application of a thin layer of the topical treatment pre-
scribed as a test dose on a non‐lesional area.
4 | Discussion
Clinical guidelines assist healthcare professionals in making
treatment decisions; however, treatment‐related decisions are
often based on patient‐specific factors, access to certain treat-
ment options, as well as the patient's medical history and
response to previous AD treatment options [6–11, 16–18].
Our assessment of the clinical practice of 17 expert derma-
tologists showed that initial pharmacologic treatment of
mild‐to‐moderate AD is consistent with current national and
international guidelines [6–11] in that most participants
recommended the use of TCSs and good skin care practices.
The overall level of agreement observed may be attributed to
the fact that these survey participants are experts who have
been involved in the development of these guidelines. Patient
age, affected body regions and disease severity were identified
as factors that influenced the potency of the TCS prescribed.
Higher‐potency TCSs were considered for older patients and
thosewithmoreseveresignsand symptoms related to AD.
Lower‐potency TCSs or non‐TCSs were commonly considered
for patients whose AD involved sensitive areas of the body.
Lengths of initial treatment of ≤4 weeks was recommended
consistent with clinical guidelines [6, 7]; however, a longer
length of treatment would be considered for patients with
greater disease severity.
A proactive approach to treatment consisting of maintenance
with topical treatment to reduce relapse of AD is currently
recommended, especially in more severe cases or resistant
forms of AD in which relapse occurs quickly after dis-
continuation of topical therapy [6, 7, 14, 20]. The results of our
questionnaire show that this approach is often used in clinical
practice but is dependent on the patient's case.
Although TCSs are regarded as the mainstay of treatment
of AD, there are certain limitations which may result in a
different topical anti‐inflammatory being prescribed [6, 7, 21].
Corticophobia and the potential adverse effects secondary to
TCS use were indicated as the main reasons for deviating from
standard treatment guidelines. Adequate patient education
and improved health literacy may be used to minimize a
patient's corticophobia [22].
Potential cutaneous adverse effects associated with the use of
TCSs include skin atrophy, purpura, telangiectasia and striae [6].
The results of the questionnaire showed that the most common
adverse effect listed as a safety concern was skin atrophy. This is
especially relevant with the use of high‐potency TCSs; long‐term
use; use of excessive quantities; occlusion; application to sensitive
areas; and/or use by patients with thinner skin including infants,
younger children and elderly patients who are generally more
susceptible to skin atrophy [6, 23, 24].
Solutions to minimizing or avoiding the adverse effects associ-
ated with TCSs include limiting long‐term continuous use and
the use of lower‐potency TCSs [6, 23]. In addition, a non‐TCS
can be used in an alternating dosing regimen with a TCS as a
steroid‐sparing agent or as monotherapy [25, 26]. A non‐TCS
also can be used in the management of flares to decrease the
need for TCSs as rescue therapy [27]. Studies have shown
7of11
TABLE 1 | Summary of management of mild‐to‐moderate AD.
Treatment period Treatment
Special reasons for deviation
from standard current
guidelines
First‐line
pharmacologic
treatment(s) for initial
control
•< 2 years: Low‐to‐medium potency TCS
•2–12 and > 12 years of age: Low‐to‐high potency TCS
○< 1 week to ≤4 weeks if mild
○> 4 weeks if severe
Note: If a sensitive region of the body is affected, use a lower potency TCS or a non‐TCS
Infection, corticophobia, lack of
improvement in disease severity,
worsening of AD, cost, access,
adverse effects secondary to
pharmacologic treatment options
The higher the AD‐related disease severity, the higher the potency of the TCS prescribed
Time to re‐evaluation •Time until re‐evaluation of treatment is guided by severity; the greater the disease severity, the shorter the time
until re‐evaluation
○1to≤4 weeks for more severe cases
○1 to 4 months for milder cases
Treatment(s) during
follow‐up period
Reactive versus proactive treatment depending on the patient's case
Discontinue topical anti‐
inflammatory therapies,
reinforce good skin care and
check adherence; reintroduce
topical anti‐inflammatory
treatments to treat flares
(reactive)
a
Continue current
treatment and
schedule a follow‐
up (proactive)
Reduce dose or
switch to non‐TCS
depending on patient
case (proactive)
Switch to
non‐TCS
(proactive)
Reduce dose
(proactive)
Treatment(s) in the
case of a flare
If flare occurs treat with 1–2 weeks of a higher potency TCS followed by a non‐TCS (pending improvement)
a
Abbreviations: AD, atopic dermatitis; TCS, topical corticosteroid.
a
Participants indicated that depending on the frequency of the flares they would consider the use of a topical anti‐inflammatory as maintenance.
8of11 JEADV Clinical Practice, 2025
significant steroid‐sparing effects with the use of TCIs (e.g.,
pimecrolimus) and emollients [25, 26, 28]. Currently, there is a
Phase 3 proof‐of‐concept trial evaluating the steroid‐sparing
effect of crisaborole in children (NCT 03832010) [29]. According
to the results of the questionnaire, non‐TCSs were not selected
as first‐line treatment options for AD; however, several parti-
cipants stated that they would prescribe lower‐potency TCSs or
non‐TCSs for sensitive regions of the body and for younger
patients who had thinner skin versus older patients. Moreover,
following the initial phase of treatment, most participants
indicated that they would utilize non‐TCSs plus TCSs in the
management of AD, often using the non‐TCS for maintenance
and treatment of flares depending on the patient's case.
TCIs are approved for short‐term and noncontinuous treatment
in recalcitrant AD and use in sensitive skin areas [6, 7, 21,
30–32]. In addition, tacrolimus is approved for the maintenance
treatment of moderate‐to‐severe AD for the prevention of flares
and the prolongation of flare‐free intervals in certain countries,
including Canada [6, 7, 30, 31]. Most participants reported that
TCIs had been approved in their region for use in patients aged
> 2 years, while almost half of participants reported that TCIs
had not been approved for use in patients aged <2 years.
Although TCIs do not cause skin atrophy, more than half of the
participants listed adverse effects including having a burning
sensation as a concern, while others listed cost. In some coun-
tries, the boxed warning associated with TCI use was also a safety
consideration for patients, although no causal relationship
between malignancy and TCIs has been established [6, 32–34].
Crisaborole ointment, 2%, is a nonsteroidal PDE4 inhibitor for the
treatment of mild‐to‐moderate AD. Countries including the Uni-
ted States and Canada have approved crisaborole for use in pa-
tients aged ≥3months[35, 36]; however, in other countries,
including Australia, crisaborole has only been approved for use in
patients aged ≥2 years. Only 4 of 17 and 2 of 17 participants
reported that crisaborole had not been approved for use in
their region of practice in patients aged < 2 and > 2 years,
respectively. Crisaborole has a favourable safety profile, with
minimal adverse effects and no boxed warnings or limitations on
the duration of use [5]; however, several participants listed adverse
effects including application site pain as a limitation and others
listed cost. In Phase 3 clinical studies, 4.4% of patients experienced
application site pain (described as a burning or stinging sensation)
which was considered to be treatment‐related [37]; application site
pain was the most common safety concern among participants.
Two topical JAKis, ruxolitinib and delgocitinib, are approved for
use in some countries, both having promising efficacy and safety
profiles [38, 39]. Ruxolitinib cream is approved in the United
States for short‐term AD and noncontinuous chronic treatment of
mild‐to‐moderate AD in non‐immunocompromised patients aged
>12years[39]. Delgocitinib is approved in Japan to treat children
and adults with AD [38, 39]. More than half of the participants
had no experience with topical JAKis, and some stated that these
agents are not available within their regions. A few participants
indicated cost as a limitation. Cardiovascular or thrombotic events
were also listed.
Mitigating adverse effects improves adherence which should
enhance patient outcomes [40]. Application site reactions
are often the most common adverse effects noted with TCS
(e.g., skin atrophy) and non‐TCSs [40]. The non‐TCSs, TCIs,
and crisaborole are more likely to cause application site pain
when applied to broken, infected or severely inflamed skin;
thus, application to these areas should be avoided [40]. To
mitigate application site reactions, participants also advised
patient education, using a TCS to calm/heal skin followed
by a non‐TCS, treatment refrigeration, use of a moisturizer,
application of a thin layer and a test dose of the treat-
ment [40].
This study has several limitations. First, these results are limited
to the practice patterns of the 17 chosen participants and,
although they are geographically diverse, several countries and
regions were not represented in this study, which further limits
the generalizability of the findings. Additionally, all participants
are from large academic/research centres, and their approaches
to the management of AD may not be universally applicable to
the practices of general physicians in smaller or more rural
settings. Finally, although the results represent practice patterns
of many countries and regions, the availability of products may
differ among countries. Moreover, despite the approval of a
topical treatment, use is often limited by patient age according
to restrictions stated in the product label for a specific country
Table 1.
5 | Conclusions
The management of mild‐to‐moderate AD in clinical practice is
influenced by several patient‐specific factors, access to treat-
ment and practical experience with the available treatment
options. A care plan tailored to patient needs and preferences
with adequate patient education and cognizance of patient‐
specific factors is needed to achieve optimized patient out-
comes. It is important that the knowledge and experience
gained from the day‐to‐day practices of specialists be evaluated
so that current guidelines might be adapted to optimally treat
AD in the future.
Author Contributions
Lawrence F. Eichenfield, Linda F. Stein Gold, Adelaide A. Hebert, Lyn
Guenther, Yuliya Valdman‐Grinshpoun, Dan Ben‐Amitai, Roni P.
Dodiuk‐Gad, Michael J. Cork, Valeria Aoki, Chia‐Yu Chu, Jianzhong
Zhang, Lin Ma, Hidehisa Saeki, Paula C. Luna, and Mark Jean‐Aan Koh
contributed equally to drafting and revising the article critically for
important intellectual content and approved the final version to be
published. All named authors meet the International Committee of
Medical Journal Editors (ICMJE) criteria for authorship for this article,
take responsibility for the integrity of the work as a whole, and have
given their approval for this version to be published.
Acknowledgements
We thank Dr. Astraf M. Reda (Mediclinic Welcare Hospital, Dubai,
United Arab Emirates; Mohammed Bin Rashid University of Medicine
and Health Sciences, Dubai, United Arab Emirates) and Dr. James
Bergman (Department of Dermatology and Skin Science, University of
British Columbia, Vancouver, British Columbia, Canada) who partici-
pated in the expert panel, completed the questionnaire and contributed
to the early development of the article. Editorial and medical writing
support under the guidance of the authors was provided by Chantell
9of11
Hayward, PharmD, and Lisa M. Klumpp Callan, PhD, at ApotheCom,
San Francisco, CA, USA, and was funded by Pfizer Inc., New York, NY,
USA, in accordance with Good Publication Practice (GPP 2022)
guidelines (Ann Intern Med. 2022; 10.7326/M22‐1460). This study was
sponsored by Pfizer Inc., New York, NY, USA.
Ethics Statement
The authors have nothing to report. This article does not contain any
studies with human participants by any of the authors. Dr. Astraf M.
Reda and Dr. James Bergman provided written informed consent to
participate in this study.
Conflicts of Interest
Lawrence F. Eichenfield has served as a consultant, speaker, advisory
board member or investigator for AbbVie, Amgen, Apogee, Arcutis,
Aslan, Attovia, Bristol Myers Squibb, Castle Biosciences, Dermavant, Eli
Lilly, Forte, Galderma, Incyte, Janssen, Johnson & Johnson, LEO
Pharma, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sanofi
Genzyme, Target RWE and UCB. Linda F. Stein Gold has received
grants from Pfizer Inc., Incyte and LEO Pharma and has received
payment for lectures from Pfizer Inc. and LEO Pharma. Adelaide A.
Hebert has received research grants from Pfizer Inc., AbbVie, Amgen
and Arcutis paid to UTHealth McGovern Medical School. She received
honoraria from Pfizer Inc., Almirall, Arcutis, Beiersdorf, Galderma,
Incyte, Novan, Ortho Dermatologics and Verrica and served on a DSMB
for Alphyn, Ortho Dermatologics and Sanofi Regeneron. Lyn Guenther
has received honoraria and/or research and/or consulting support from
Pfizer Inc., AbbVie, Actilion, Amgen, Aralez, Bausch Health, BMS,
Boehringer Ingelheim, Celgene, Cipher, Eli Lilly and Company, Gal-
derma, GSK, Incyte, Innovaderm, Janssen, Johnson & Johnson, La
Roche‐Posay, LEO Pharma, Merck, Miravo, Novartis and UCB. She has
served as a member of a speaker's bureau/advisory board for Pfizer Inc.,
AbbVie, Actilion, Amgen, Altana, Aralez, ASLAN Pharmaceuticals,
Bausch Health, Eli Lilly and Company, Galderma, Janssen, Johnson &
Johnson, La Roche‐Posay, LEO Pharma, Novartis, Sanofi Aventis and
UCB. Yuliya Valdman‐Grinshpoun has served as an advisor and/or paid
speaker and/or participated in clinical trials sponsored by AbbVie,
Amgen, Boehringer Ingelheim, Celgene, Dexcel, Eli Lilly and Company,
Kamada, Janssen, Neopharm, Novartis, Perrigo, Pierre Fabre, Rafa,
Sanofi and Teva. Roni P. Dodiuk‐Gad has served as an advisor and/or
paid speaker and/or participated in clinical trials sponsored by Pfizer
Inc., AbbVie, Dexcel, Eli Lilly and Company, Janssen, Novartis, Sanofi
and La Roche‐Posay. Michael J. Cork has served as a clinical trial
investigator for Pfizer Inc., Atopix, Galapagos, Hyphens, Johnson &
Johnson, Kymab, LEO Pharma, L'Oreal/La Roche‐Posay, Novartis,
Regeneron and Sanofi Genzyme. He has served as an advisory board
member, consultant and/or invited lecturer for Pfizer Inc., AbbVie,
Amlar, Astellas, Atopix, Boots, Dermavant, Galapagos, Galderma,
Hyphens, Johnson & Johnson, Kymab, Leo, L'Oreal/La Roche‐Posay,
Menlo, Novartis, Oxagen, Procter & Gamble, Reckitt Benckiser, Re-
generon and Sanofi Genzyme. Valeria Aoki has served as a clinical trial
investigator for Eli Lilly and Company and Sanofi Genzyme and has
served as an advisory board member, consultant and/or invited lecturer
for Pfizer Inc., AbbVie, Galderma and LEO Pharma. Chia‐Yu Chu has
served as a clinical trial investigator and/or consultant and/or speaker
for Pfizer Inc., AbbVie, Amgen, Dermira, Eli Lilly and Company, GSK,
Kymab, Mylan, Novartis, Oneness Biotech, Regeneron, Roche, Sanofi
and Viatris. He has served on the advisory boards of Pfizer Inc., AbbVie,
Eli Lilly and Company, Mylan, Roche and Sanofi. Jianzhong Zhang and
Lin Ma have received speaking and consulting support from Pfizer Inc.
Hidehisa Saeki has received lecturing support from AbbVie GK, Eli Lilly
Japan K.K., Japan Tobacco Inc., Kyowa Kirin Co. Ltd., LEO Pharma
K.K., Maruho Co. Ltd., Mitsubishi Tanabe Pharma Corporation, No-
vartis Pharma K.K., Otsuka Pharmaceutical Co. Ltd., Sanofi K.K., Taiho
Pharmaceutical Co. and Torii Pharmaceutical Co. Ltd. and has received
clinical research and/or grant support from AbbVie GK, Esai Co. Ltd.,
LEO Pharma K.K. and Maruho Co. Ltd., Taiho Pharmaceutical Co. and
Tokiwa Pharmaceutical Co. Ltd. Paula C. Luna has received lecturing
and/or consulting and/or honoraria and/or grant support from Pfizer
Inc., AbbVie, Amgen, Beiersdorf, Boehringer Ingelheim, Bristol Myers
Squibb, Elli Lilly and Company, GlaxoSmithKline, Janssen, Laboratoire
La Roche‐Posay, Novartis, Pierre Fabre Laboratory, Sanofi Genzyme
and Takeda. Mark Jean‐Aan Koh has served as a speaker and/or
received research support from Pfizer Inc., AbbVie, Amryt, ASLAN
Pharmaceuticals, Bioderma/Naos, DKSH, Ego, Eli Lilly and Company,
Galderma, Good Pharma, GSK, Hyphens, LEO Pharma, Lion, L'Oréal/
La Roche‐Posay, Menarini, Novartis, Quoin and Sanofi. Dan Ben‐
Amitai declares no conflicts of interest.
Data Availability Statement
Upon request, and subject to review, Pfizer will provide the data that
support the findings of this study. Subject to certain criteria, conditions
and exceptions, Pfizer may also provide access to the related individual
deidentified participant data. See https://www.pfizer.com/science/
clinical-trials/trial-data-and-results for more information.
References
1. T. Bieber, “Atopic Dermatitis,”Annals of Dermatology 22, no. 2
(2010): 125–137.
2. J. I. Silverberg, J. M. Gelfand, D. J. Margolis, et al., “Patient Burden
and Quality of Life in Atopic Dermatitis in US Adults,”Annals of
Allergy, Asthma & Immunology 121 (2018): 340–347.
3. C. H. Na, J. Chung, and E. L. Simpson, “Quality of Life and Disease
Impact of Atopic Dermatitis and Psoriasis on Children and Their
Families,”Children 6 (2019): 133.
4. J. P. Thyssen, A. S. Halling, P. Schmid‐Grendelmeier, E. Guttman‐
Yassky, and J. I. Silverberg, “Comorbidities of Atopic Dermatitis: What
Does the Evidence Say?,”Journal of Allergy and Clinical Immunology
151 (2023): 1155–1162.
5. M. Boguniewicz, L. Fonacier, E. Guttman‐Yassky, P. Y. Ong,
J. Silverberg, and J. R. Farrar, “Atopic Dermatitis Yardstick: Practical
Recommendations for an Evolving Therapeutic Landscape,”Annals of
Allergy, Asthma & Immunology 120 (2018): 10–22.e2.
6. R. Sidbury, A. Alikhan, L. Bercovitch, et al., “Guidelines of Care
for the Management of Atopic Dermatitis in Adults With Topical Thera-
pies,”Journal of the American Academy of Dermatology 89 (2023): e1–e20.
7. A. Wollenberg, M. Kinberger, B. Arents, et al., “European Guideline
(EuroGuiDerm) on Atopic Eczema: Part II: Non‐Systemic Treatments
and Treatment Recommendations for Special AE Patient Populations,”
Journal of the European Academy of Dermatology and Venereology 36
(2022): 1904–1926.
8. V. Aoki, D. Lorenzini, R. L. Orfali, et al., “Consensus on the Thera-
peutic Management of Atopic Dermatitis: Brazilian Society of Derma-
tology,”Anais Brasileiros De Dermatologia 94 (2019): 67–75.
9. A. M. Reda, A. Elgendi, A. I. Ebraheem, et al., “A Practical Algorithm
for Topical Treatment of Atopic Dermatitis in the Middle East Em-
phasizing the Importance of Sensitive Skin Areas,”Journal of
Dermatological Treatment 30 (2019): 366–373.
10. T. C. Chan, N. L. Wu, L. S. Wong, et al., “Taiwanese Dermatological
Association Consensus for the Management of Atopic Dermatitis: A
2020 Update,”Journal of the Formosan Medical Association 120 (2021):
429–442.
11. T. C. Yao, I. J. Wang, H. L. Sun, et al., “Taiwan Guidelines for the
Diagnosis and Management of Pediatric Atopic Dermatitis: Consensus
Statement of the Taiwan Academy of Pediatric Allergy, Asthma and
Immunology,”Journal of Microbiology, Immunology and Infection 55
(2022): 561–572.
12. E. Kleinman, J. Laborada, L. Metterle, and L. F. Eichenfield, “What's
New in Topicals for Atopic Dermatitis?,”American Journal of Clinical
Dermatology 23 (2022): 595–603.
10 of 11 JEADV Clinical Practice, 2025
13. A. Papier and L. C. Strowd, “Atopic Dermatitis: A Review of Topical
Nonsteroid Therapy,”Drugs in Context 7 (2018): 1–10.
14. G. Girolomoni and V. M. Busà, “Flare Management in Atopic
Dermatitis: From Definition to Treatment,”Therapeutic Advances in
Chronic Disease 13 (2022): 20406223211066728.
15. T. Czarnowicki, H. He, J. G. Krueger, and E. Guttman‐Yassky,
“Atopic Dermatitis Endotypes and Implications for Targeted Ther-
apeutics,”Journal of Allergy and Clinical Immunology 143 (2019): 1–11.
16. V. C. Correa, L. H. Lugo‐Agudelo, D. C. Aguirre‐Acevedo, et al.,
“Individual, Health System, and Contextual Barriers and Facilitators for
the Implementation of Clinical Practice Guidelines: A Systematic Me-
tareview,”Health Research Policy and Systems 18 (2020): 74.
17. J. Thyssen, T. Berents, M. Bradley, et al., “Clinical Management of
Atopic Dermatitis in Adults: Mapping of Expert Opinion in 4 Nordic
Countries Using a Modified Delphi Process,”Acta Dermato
Venereologica 100 (2020): 1–11.
18. M. Hashemiparast, R.Negarandeh, and D. Theofanidis, “Exploring the
Barriers of Utilizing Theoretical Knowledge in Clinical Settings: A Qual-
itative Study,”International Journal of Nursing Sciences 6 (2019): 399–405.
19. S. Gabros, T. A. Nessel, and P. M. Zito, Topical Corticosteroids
(Treasure Island [FL]: StatPearls Publishing, 2022).
20. A. Wollenberg and T. Bieber, “Proactive Therapy of Atopic Der-
matitis: An Emerging Concept,”Allergy 64 (2009): 276–278.
21. L. McDowell and B. Olin, “Crisaborole: A Novel Nonsteroidal
Topical Treatment for Atopic Dermatitis,”Journal of Pharmacy
Technology 35 (2019): 172–178.
22. T. F. Gomes, K. Kieselova, V. Guiote, M. Henrique, and F. Santiago,
“A Low Level of Health Literacy Is a Predictor of Corticophobia in
Atopic Dermatitis,”Anais Brasileiros De Dermatologia 97 (2022):
704–709.
23. E. Axon, J. R. Chalmers, M. Santer, et al., “Safety of Topical Corti-
costeroids in Atopic Eczema: An Umbrella Review,”BMJ Open 11
(2021): e046476.
24. R. Tanei, “Atopic Dermatitis in Older Adults: A Review of Treat-
ment Options,”Drugs & Aging 37 (2020): 149–160.
25. M. M. Y. El‐Batawy, M. A. W. Bosseila, H. M. Mashaly, and
V. S. G. A. Hafez, “Topical Calcineurin Inhibitors in Atopic Dermatitis:
A Systematic Review and Meta‐Analysis,”Journal of Dermatological
Science 54 (2009): 76–87.
26. R. Grimalt, V. Mengeaud, and F. Cambazard, “The Steroid‐Sparing
Effect of an Emollient Therapy in Infants With Atopic Dermatitis: A
Randomized Controlled Study,”Dermatology 214 (2007): 61–67.
27. T. Luger, A. S. Paller, A. D. Irvine, et al., “Topical Therapy of Atopic
Dermatitis With a Focus on Pimecrolimus,”Journal of the European
Academy of Dermatology and Venereology 35 (2021): 1505–1518.
28. T. Zuberbier, L. Heinzerling, T. Bieber, U. Schauer, S. Klebs, and
M. Bräutigam, “Steroid‐Sparing Effect of Pimecrolimus Cream 1% in
Children With Severe Atopic Dermatitis,”Dermatology 215 (2007):
325–330.
29. US National Library of Medicine,Steroid‐Reducing Effects of Crisa-
borole (Bethesda, MD: US National Library of Medicine, 2022).
30. Astellas Ireland Co. Ltd., Protopic 0.03% Ointment (SPC) (Kerry,
Ireland: Astellas Ireland Co. Ltd, 2022).
31. LEO Pharma Inc., Protopic Tacrolimus Ointment 0.03% and 0.1%
(w/w) Topical Calcineurin Inhibitor ATC Code: D11AH01 (Thornhill,
Ontario, Canada: LEO Pharma Inc., 2016).
32. L. F. Eichenfield, W. L. Tom, T. G. Berger, et al., “Guidelines of Care
for the Management of Atopic Dermatitis2. Management and Treat-
ment of Atopic Dermatitis With Topical Therapies,”Journal of the
American Academy of Dermatology 71 (2014): 116–132.
33. M. Lam, J. W. Zhu, M. Tadrous, and A. M. Drucker, “Association
Between Topical Calcineurin Inhibitor Use and Risk of Cancer,
Including Lymphoma, Keratinocyte Carcinoma, and Melanoma: A
Systematic Review and Meta‐Analysis,”JAMA Dermatology 157 (2021):
549–558.
34. M. M. Asgari, A. L. Tsai, L. Avalos, M. Sokil, and
C. P. Quesenberry Jr., “Association Between Topical Calcineurin
Inhibitor Use and Keratinocyte Carcinoma Risk Among Adults With
Atopic Dermatitis,”JAMA Dermatology 156 (2020): 1066–1073.
35. Pfizer Labs, EUCRISA (Crisaborole) Ointment, for Topical Use (New
York, NY: Pfizer Labs, 2023).
36. Pfizer Canada Inc., EUCRISA
TM
(Crisaborole) Ointment, 2% for
Topical Use Phosphodiesterase‐4 (PDE‐4) Inhibitor (Kirkland, Quebec:
Pfizer Canada Inc., 2018), 20.
37. A. S. Paller, W. L. Tom, M. G. Lebwohl, et al., “Efficacy and Safety of
Crisaborole Ointment, a Novel, Nonsteroidal Phosphodiesterase 4
(PDE4) Inhibitor for the Topical Treatment of Atopic Dermatitis (AD)
in Children and Adults,”Journal of the American Academy of
Dermatology 75 (2016): 494–503.e6.
38. R. Chovatiya and A. S. Paller, “JAK Inhibitors in the Treatment of
Atopic Dermatitis,”Journal of Allergy and Clinical Immunology 148
(2021): 927–940.
39. N. Sideris, E. Paschou, K. Bakirtzi, et al., “New and Upcoming
Topical Treatments for Atopic Dermatitis: A Review of the Literature,”
Journal of Clinical Medicine 11 (2022): 4974.
40. S. Madsen, K. N. Price, V. Y. Shi, and P. A. Lio, “Pearls in Mitigating
Application Pain of Topical Nonsteroidal Agents,”Dermatology 236
(2020): 477–480.
Supporting Information
Additional supporting information can be found online in the
Supporting Information section.
11 of 11
