Different strategies for using topical corticosteroids for established eczema (Protocol) Different...

Different strategies for using topical corticosteroids for

established eczema (Protocol)

Moed H, Yang Q, Oranje AP, Panda S, van der Wouden JC

This is a reprint of a Cochrane protocol, prepared and maintained by The Cochrane Collaboration and published in The Cochrane

Library 2012, Issue 10

http://www.thecochranelibrary.com

Different strategies for using topical corticosteroids for established eczema (Protocol)

Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

http://www.thecochranelibrary.com

T A B L E O F C O N T E N T S

1HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

6ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

6REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

8APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

9HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

9CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

9DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

iDifferent strategies for using topical corticosteroids for established eczema (Protocol)


[Intervention Protocol]

Different strategies for using topical corticosteroids forestablished eczema

Heleen Moed1, Quan Yang2, Arnold P Oranje3, Saumya Panda4, Johannes C van der Wouden5

1Department of General Practice, Erasmus MC, Rotterdam, Netherlands. 2Department of Pharmacy and Pharmacology, University

of Bath, Bath, UK. 3Pediatric Dermatology Division, Department of Pediatrics and KinderHaven, Erasmus MC, University Medical

Center, Havenziekenhuis, Rotterdam, Netherlands. 4Department of Dermatology, KPC Medical College and Hospital, Kolkata, India.5Department of General Practice and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam,

Netherlands

Contact address: Heleen Moed, Department of General Practice, Erasmus MC, PO Box 2040, Room GK 1051, Rotterdam, 3000 CA,

Netherlands. [email protected].

Editorial group: Cochrane Skin Group.

Publication status and date: New, published in Issue 10, 2012.

Citation: Moed H, Yang Q, Oranje AP, Panda S, van der Wouden JC. Different strategies for using topical corticosteroids for established

eczema. Cochrane Database of Systematic Reviews 2012, Issue 10. Art. No.: CD010080. DOI: 10.1002/14651858.CD010080.


A B S T R A C T

This is the protocol for a review and there is no abstract. The objectives are as follows:

To assess the best application strategies of topical corticosteroids for treating established eczema in people of all ages.

1Different strategies for using topical corticosteroids for established eczema (Protocol)


mailto:[email protected]

B A C K G R O U N D

Description of the condition

Eczema (a synonym of atopic eczema or atopic dermatitis) is a

non-infective, chronic, inflammatory skin disease that affects -

worldwide - 7% to 15% of children and 2% to 10% of adults

(Dirven-Meijer 2008; Williams 2008). Two-thirds of people with

the condition have a family history of eczema, asthma, or hay

fever. The cause of eczema is complex and poorly-understood.

It is thought to be a result of both genetic predisposition and

environmental factors (Cork 2009).

To be precise, the term ’atopic eczema’ should only refer to indi-

viduals who have the physical features of eczema plus evidence of

specific immunoglobulin E (IgE) antibodies to common environ-

mental allergens, such as house dust mites (Flohr 2004). How-

ever, up to 40% of children with atopic eczema are not atopic

when defined according to allergy tests, such as skin prick tests

(Bohme 2001). Others have found that up to two-thirds of peo-

ple with atopic dermatitis are not atopic (Flohr 2004), implying

that continued use of the term ’atopic dermatitis’ is problematic.

A revised nomenclature for allergy (Johansson 2001) has been up-

dated by the World Allergy Organization (Johansson 2004). The

term ’eczema’ is proposed to replace the provisional term ’atopic

eczema/dermatitis syndrome’ (AEDS) and can be split into ’atopic

eczema’ and ’non-atopic eczema’. We use the term ’eczema’ in this

protocol.

Clinical features

Eczema may be acute (short and severe) with weeping vesicles

on red, swollen skin, or it may be chronic (long-term) with (be-

sides red, swollen skin) also lichenification (thickening of the skin

caused by repeated rubbing or scratching), excoriation (abrasion

as a result of rubbing or scratching), hyperpigmentation, and ex-

aggerated surface markings. Although the scaly patches or lesions

can be located anywhere on the body, the distribution and type

of lesions vary at different stages of life. In general, the condition

mainly affects the stretch sites of the extremities and face in in-

fants. At about two years of age, the lesions mainly appear on the

limbs, particularly at the creases of the elbows and knees, as well

as the neck, wrists, and ankles. In adulthood, the lesions become

more widespread than those seen in childhood.

The severity of eczema is extremely variable, ranging from an occa-

sionally dry, localised, mild scaly patch to generalised involvement

of the whole body, which becomes covered with red, oozing, in-

fected lesions. And its course may be continuous for prolonged pe-

riods or of a relapsing-remitting nature. Itching induces a vicious

cycle of scratching, leading to skin damage, which in turn causes

itchiness - the so called “itch-scratch” cycle (Sugimoto 2007).

There is a tendency to develop dry, sensitive skin in adulthood,

even in those who have ’grown out’ of eczema. This is thought

to be due to a weakened skin barrier function caused by genetic

predisposition (Cork 2009). Thus, the skin may be prone to in-

flammation in the presence of environmental insults, such as soaps

and detergents, washing with hard water, and exposure to house

dust mites (Cork 2009).

Description of the intervention

Although eczema cannot be cured, symptoms can be allevi-

ated with a wide range of treatment choices (Darsow 2010;

Traidl-Hoffmann 2010). These include emollients, (topical) corti-

costeroids, topical coal tar preparations, and topical calcineurin in-

hibitors (such as tacrolimus and pimecrolimus). Other treatment

methods, such as wet-wrap treatment, phototherapy, and com-

plementary therapies (Chang 2007), are also used in severe cases

where there has been a limited response to traditional treatments.

People with established eczema and parents of affected children

often also use alternative treatments.

The aims of treatment are to keep skin healthy, prevent flare-

up, and treat symptoms as soon as they occur. The majority of

people with mild to moderate eczema control their symptoms

by daily application of emollients (with or without antibacterial

additives) (Oranje 2010) accompanied by symptomatic anti-in-

flammatory therapy consisting of topical corticosteroids (Grimalt

2007). For moderate to severe eczema, treatment in the form of

short-burst oral systemic corticosteroids or systemic immunosup-

pressants, such as cyclosporin A, is used under the care of a spe-

cialist.

Why it is important to do this review

Topical corticosteroids of different potencies are the mainstay of

treatment for eczema. A stepwise approach in which treatment

steps are tailored to the severity of the disease is advocated (Baumer

2008; Lewis-Jones 2007). There are different strategies of using

topical corticosteroids in eczema. According to the reactive thera-

peutic approach, people are given anti-inflammatory agents at the

onset of flare-up episodes, and this is stopped after several days or

weeks when eczema is under control. Nowadays, it is suggested

that proactive treatment is more beneficial than the commonly-

used reactive approach (Bieber 2010). The concept of proactive

treatment involves initial high-dose therapy followed by a long-

term low-dose treatment to sustain the remission state.

Another aspect of treating eczema is the stepped approach to man-

aging the disease. Management can then be stepped up or down,

according to the severity of symptoms. Potency of the steroids can

be increased when low-dose therapy is insufficient (step-up), or

symptoms can directly be treated with a high potency of steroids

followed by gradually lowering the potency (step-down) (Nice

CG57 2007).

The frequency of application (once-daily versus more frequent

use) is another aspect of using corticosteroids in an optimal way,



as is duration of treatment and using different formulations of the

same molecule. It should be clearly stated that, as of now, there is

no clear answer regarding the best strategy to treat eczema.

Another aspect that plays an important role in treating eczema with

topical steroids is concern over the safety of topical corticosteroid

application in children (Bewley 2008; Smith 2010). This may

lead to the use of mild-potency medications and poor adherence

to treatment, hence, increasing the risk of poor clinical response

and treatment failure (Aubert-Wastiaux 2011). This may, in turn,

cause poor symptom-control and reduced quality of life.

Overall, a systematic review of the best strategies for using topical

corticosteroids in the treatment of established eczema is therefore

required.

O B J E C T I V E S

To assess the best application strategies of topical corticosteroids

for treating established eczema in people of all ages.

M E T H O D S

Criteria for considering studies for this review

Types of studies

All randomised controlled trials (RCTs) comparing different

strategies for administering topical corticosteroids for treating

eczema.

Types of participants

Included studies will include the following:

• participants with established eczema that has been

diagnosed by a medical practitioner. We will regard diagnostic

criteria such as the Hanifin and Rajka definition (Hanifin 1980)

or the UK modification (Williams 1994) as acceptable, as well as

diagnosis of eczema by a dermatologist using the terms ’atopic

eczema’ or ’atopic dermatitis’.

• participants of all ages. We will perform subgroup analyses

for different age categories (only if a minimum of five studies per

age stratum can be included for the primary outcome). We will

draw a distinction between infants (0 to 2 years), children (2 to

12 years - we plan to undertake 2 subgroup analyses looking at

children aged 2 - 5 years and aged 5 - 12 years), adolescents (12

to 18 years), and adults (> 18 years).

The review will exclude studies that include participants with other

types of eczema, such as contact dermatitis, seborrhoeic eczema,

varicose eczema, and discoid eczema.

Types of interventions

We will make the following comparisons with respect to applica-

tion methods:

• duration of treatment (short-term period of a maximum of

four weeks versus long-term period for more than four weeks);

• frequency of treatment (once-daily versus more frequent

application);

• step-up or step-down treatment (increasing potency when

symptoms flare up versus starting with high potency and

gradually lowering potency);

• potency of steroids (long bursts of weak steroids versus

short bursts of strong steroids); and

• reactive or proactive treatment (reactive treatment, which is

the use of corticosteroids in response to symptoms and flare-ups

(started as soon as symptoms appear and continued only for

several days after symptoms subside) versus proactive treatment,

which is intensive corticosteroid therapy until visible skin lesions

have cleared followed by continuous low-level use of

corticosteroids to the previously-affected skin area).

In order to define potency of corticosteroids, there are two dif-

ferent systems (the seven-group US system and the four-group

European system). To avoid confusion, we will use the Euro-

pean system to define steroid potency (class I is mild, class II is

moderate, class III is potent, and class IV is very potent) (http://

www.topicalsteroids.co.uk).

Types of outcome measures

Primary outcomes

1) Changes in clinical severity of the disease as measured by vali-

dated scoring systems.

(We will use validated scoring systems, as described by the Harmo-

nizing Outcome Measures for Eczema (HOME) initiative, which

has a primary goal of facilitating an international, multidisci-

plinary consensus on core outcome measures for eczema. Exam-

ples of severity scales include SCORAD (SCORing Atopic Der-

matitis) (objective/index/patient-oriented) (Charman 2003; Kunz

1997; Oranje 2007), the EASI (Eczema Area and Severity In-

dex) (Hanifin 2001), POEM (Patient-Oriented Eczema Measure)

(Charman 2004), and the TIS score (Three Item Severity score)

(Oranje 2007; Willemsen 2009; Wolkerstorfer 1999).)

2) Disease-specific quality of life as measured by validated scoring

systems.

(We will use validated scoring systems as described by the

HOME initiative (examples of quality of life (QoL) scores in-

clude the Dermatitis Family Impact (DFI) questionnaire (Lawson

1998), the Children’s Dermatology Life Quality Index (CDLQI)

(Lewis-Jones 1995), the Quality of Life Index for Atopic Dermati-

tis (QoLIAD) (Whalley 2004), the Childhood Atopic Dermati-

tis Impact Scale (CADIS) (Chamlin 2007), and the Infants’ Der-

matitis Quality of Life Index (IDQOL) (Lewis-Jones 2001).)



http://www.topicalsteroids.co.uk/



http://www.homeforeczema.org/

Secondary outcomes

1) Global assessment by participant/parent.

2) Side-effects of topical corticosteroids (such as skin thinning,

bruising, perioral dermatitis, folliculitis, pruritus, allergic contact

dermatitis, the spread of fungal infection, hypothalamic-pituitary-

adrenal (HPA) suppression, glaucoma, and cataracts when used

around the eyes). We will only report on side-effects identified in

the included trials.

3) Participant-preference measures.

4) Relapse/flare-up rate (defined as an episode requiring escalation

of treatment or additional medical advice (Langan 2006)).

Search methods for identification of studies

We aim to identify all relevant randomised controlled trials (RCTs)

regardless of language or publication status (published, unpub-

lished, in press, or in progress).

Electronic searches

We will search the following databases:

• the Cochrane Skin Group Specialised Register;

• the Cochrane Central Register of Controlled Trials

(CENTRAL) in The Cochrane Library;

• the GREAT database (Global Resource of EczemA Trials,

from 2000);

• MEDLINE (from 1946);

• EMBASE (from 1974); and

• LILACS (Latin American and Caribbean Health Science

Information Database, from 1982).

We have devised a draft search strategy for randomised con-

trolled trials (RCTs) for MEDLINE (OVID), which is displayed

in Appendix 1. We will use this as the basis for search strategies

for the other databases listed.

Adverse Effects

We will not perform a separate search for adverse effects of the

target intervention. However, we will examine data on adverse

effects from the included studies we identify.

Searching other resources

We will search the following ongoing trials registers using the terms

’eczema’ and ’corticosteroids’:

• The metaRegister of Controlled Trials (www.controlled-

trials.com).

• The US National Institutes of Health Ongoing Trials

Register (www.clinicaltrials.gov).

• The Australian New Zealand Clinical Trials Registry (

www.anzctr.org.au).

• The World Health Organization International Clinical

Trials Registry platform (www.who.int/trialsearch).

• The EU Clinical Trials Register (https://

www.clinicaltrialsregister.eu/).

Unpublished and grey literature

We will obtain unpublished trials, ongoing trials, and grey liter-

ature via correspondence with pharmaceutical companies and in-

vestigators in the field.

We will handsearch the conference proceedings of the following

dermatology meetings from 2010 to 2012 for references to RCTs:

• EADV Congress (European Academy of Dermatology and

Venereology);

• ESDR Congress (European Society for Dermatological

Research);

• International Congress of Dermatology (ICD) from the

International Society of Dermatology (ISD);

• SID (Society for Investigative Dermatology);

• International Investigative Dermatology (IID); and

• the World Congress of Dermatology (WCD), organised by

the International League of Dermatological Societies (ILDS).

Where appropriate, we will contact the trial authors for further

information.

References from published studies

We will check the bibliographies of included studies for further

references to relevant trials.

Data collection and analysis

Selection of studies

In pairs, HM, QY, and SP will independently check titles and

abstracts identified from the searches. If it is clear that a study does

not refer to a RCT, we shall exclude the study. The same three

authors (HM, QY, and SP), in pairs, will independently assess the

full text of all RCTs of possible relevance. The authors will decide

which of the trials fit the pre-defined selection criteria, and they

will make a record of their methodological quality. The authors

will resolve any disagreement by discussion, with recourse to a

third author (APO) for arbitration, where necessary. Where there

are missing data from the trials, we will attempt to obtain the

data by contacting the author. We will list excluded studies in the

’Characteristics of excluded studies’ tables.

Data extraction and management

HM, QY, SP, and APO, in pairs, will independently extract data

onto a specially-designed data extraction sheet. HM will collect all



http://www.controlled-trials.com/

http://www.controlled-trials.com/

http://www.clinicaltrials.gov/

http://www.anzctr.org.au/

http://www.who.int/ictrp/search/en/

http://www.who.int/ictrp/search/en/

https://www.clinicaltrialsregister.eu/



data to compare results and resolve any differences of opinion. If

required, QY and HM will write to authors requesting additional

information. We will enter data into Review Manager (RevMan).

Assessment of risk of bias in included studies

The quality assessment will include an evaluation of the following

components for each included study:

(a) the method of generation of the randomisation sequence;

(b) the method of allocation concealment - we will consider it

’adequate’ if the assignment could not be foreseen;

(c) who was blinded/not blinded (participants, clinicians, outcome

assessors);

(d) how many participants were lost to follow up in each arm, and

whether reasons for losses were adequately reported; and

(e) whether participants were analysed in the groups to which they

were originally randomised (intention-to-treat).

In addition, we shall also report on the following:

(f ) the criteria used to diagnose eczema. Where the criteria of

Hanifin and Rajka or those of Williams have been used, we shall

rate these as superior (Hanifin 1980; Williams 1994);

(g) the baseline characteristics of the participants regarding age,

sex, duration, location, and severity of eczema. We will only use

standardised scoring systems of severity of eczema (standardised

criteria such as SCORAD, TIS, POEM, and EASI) (Charman

2003; Charman 2004; Hanifin 2001; Kunz 1997; Oranje 2007;

Willemsen 2009; Wolkerstorfer 1999);

(h) drug identity (type of corticosteroid with class or other prepa-

ration), formula, ointment or cream, source, dose, frequency and

duration of treatment, and instructions;

(i) whether outcome measures were described and their assessment

was standardised;

(j) whether concomitant anti-eczema treatment was used/permit-

ted or standardised; and

(k) the use and appropriateness of statistical analyses, where tabu-

lated data cannot be extracted from the original publication.

We will record information on all of these components in ’Risk of

bias’ tables, which will form part of the ’Characteristics of included

studies’ tables.

In pairs, HM, QY, and SP will independently assess risk of bias:

They will not be masked to study details. They will resolve any

disagreements about their ’Risk of bias’ assessments by discussion

and, if necessary, with the involvement of a third author (APO or

JCvdW).

Measures of treatment effect

When appropriate, for studies with a similar type of intervention,

we will perform a meta-analysis to calculate a weighted treatment

effect across trials using a random-effects model.

For continuous data, we will calculate mean differences (MD)

where studies use the same outcome measure, or we will calculate

standardised mean differences where studies use different outcome

measures. In either case, we will report them with 95% confidence

intervals (CI).

For dichotomous outcomes, we will express results as risk ratios

(RR) with 95% CI. We will also express the results for dichoto-

mous outcomes as number needed to treat (NNT), where appro-

priate, with a 95% CI and the baseline risk to which it applies.

Unit of analysis issues

Where there are multiple intervention groups within a trial, we will

make pair-wise comparisons of interventions versus conventional

treatment or another intervention.

For cross-over studies, we will use results of paired analyses, ex-

tracting treatment effect, standard error, and within-participant

correlation between the treatment periods (rho) from papers.

We will adopt a similar approach for within-patient studies (e.g.

right side versus left side of the same participant), although it is

unlikely that we will find such studies due to problems of systemic

contamination.

Dealing with missing data

We will contact trial authors or sponsors of studies less than 15

years old to provide details about study design or missing statistics

(mean, standard deviations). If the authors do not respond within

a reasonable time (six to eight weeks), we will conduct the review

based on available information.

For dichotomous outcomes, we will regard participants with miss-

ing outcome data as treatment failures and include these in the

analysis. For continuous outcomes, we will carry forward the last

recorded value for participants with missing outcome data.

Assessment of heterogeneity

We will assess statistical heterogeneity using the I² statistic. If the

I² statistic is less than 50%, we will synthesise data using meta-

analysis techniques. If substantial heterogeneity (I² statistic > 75%)

exists between studies for the primary outcome, we will explore

reasons for heterogeneity, such as disease severity, dosage etc.

We will explore any statistical or clinical heterogeneity using sen-

sitivity or subgroup analyses (see below). Wherever possible, we

will conduct quantitative analyses of outcomes on an intention-

to-treat basis, i.e. we will evaluate participants in the groups to

which they were randomised, rather than according to the actual

treatment that they received.

Assessment of reporting biases

We will assess publication bias graphically using funnel plots where

there are sufficient included studies (at least 10) and adequate data

are available for similar interventions.



Data synthesis

For studies with the same intervention or with a similar active com-

ponent, we will perform a meta-analysis to calculate a weighted

treatment effect across trials, using a random-effects model. Where

it is not possible to perform a meta-analysis, we will summarise -

and describe qualitatively - the data for each trial. We will not pool

cross-over studies together with parallel studies; we will deal with

these separately, as advised by the Cochrane Handbook for System-

atic Reviews of Interventions (Chapter 16.4.7, Higgins 2011). We

will adopt a similar approach for split body-part designs.

Subgroup analysis and investigation of heterogeneity

We will perform subgroup analyses where adequate information is

given; these will only be performed when at least five studies can

be found for a subgroup.

The planned subgroups are as follows:

• age - we will draw distinctions between infants (0 to 2

years), children (2 to 5 years/5 to 12 years), adolescents (12 to 18

years), and adults (> 18 years);

• application methods - frequency of application (once-daily

versus twice-daily application), reactive treatment/proactive

treatment, duration of treatment (short-term period of maximal

four weeks versus long-term period for more than four weeks),

potency of steroids (long bursts of weak steroids versus short

bursts of strong steroids); and

• severity of atopic dermatitis (mild/moderate/severe).

Sensitivity analysis

We plan to conduct sensitivity analysis to examine the effects of

excluding poor-quality studies, defined as those with a moderate

or high risk of bias as described in the Cochrane Handbook for

Systematic Reviews of Interventions (Higgins 2011).

Other

Where there is uncertainty, we will contact authors for clarifica-

tion. A consumer co-author is part of the review team, and she

will focus her help particularly on the readability and clarity of the

final review.

A C K N O W L E D G E M E N T S

The authors would like to thank Elizabeth Doney, who developed

the search strategy for MEDLINE, as well as Binbin Lu, who

commented on early drafts of the protocol.

The Cochrane Skin Group editorial base wishes to thank Hywel

Williams who was the Key Editor for this review; Matthew Grainge

and Philippa Middleton who were the Statistical and Methods

Editors, respectively; the clinical referee, Phyllis Spuls; and the

consumer referee, Michele Luke.

R E F E R E N C E S

Additional references

Aubert-Wastiaux 2011

Aubert-Wastiaux H, Moret L, Le Rhun A, Fontenoy AM,

Nguyen JM, Leux C, et al.Topical corticosteroid phobia

in atopic dermatitis: a study of its nature, origins and

frequency. The British Journal of Dermatology 2011;165(4):

808–14. [PUBMED: 21671892]

Baumer 2008

Baumer JH. Atopic eczema in children, NICE. Archives

of Disease in Childhood 2008;93(3):93–7. [PUBMED:

18495900]

Bewley 2008

Bewley A, Dermatology Working Group. Expert consensus:

time for a change in the way we advise our patients to use

topical corticosteroids. The British Journal of Dermatology

2008;158(5):917–20. [PUBMED: 18294314]

Bieber 2010

Bieber T. Clinical and subclinical inflammation in atopic

dermatitis - Implications for management. European

Dermatology 2010;5:28–31.

Bohme 2001

Bohme M, Svensson A, Kull I, Nordvall SL, Wahlgren CF.

Clinical features of atopic dermatitis at two years of age:

a prospective, population-based case-control study. Acta

Dermato-Venereologica 2001;81(3):193–7. [PUBMED:

11558876]

Chamlin 2007

Chamlin SL, Lai JS, Cella D, Frieden IJ, Williams ML,

Mancini AJ, et al.Childhood Atopic Dermatitis Impact

Scale: reliability, discriminative and concurrent validity,

and responsiveness. Archives of Dermatology 2007;143(6):

768–72. [PUBMED: 17576944]

Chang 2007

Chang C, Keen CL, Gershwin ME. Treatment of eczema.

Clinical Reviews in Allergy and Immunology 2007;33(3):

204–25. [PUBMED: 18163227]

Charman 2003

Charman C, Chambers C, Williams H. Measuring atopic

dermatitis severity in randomized controlled clinical trials:

what exactly are we measuring?. The Journal of Investigative

Dermatology 2003;120(6):932–41. [PUBMED: 12787117]



Charman 2004

Charman CR, Venn AJ, Williams HC. The patient-oriented

eczema measure: development and initial validation of a

new tool for measuring atopic eczema severity from the

patients’ perspective. Archives of Dermatology 2004;140

(12):1513–9. [PUBMED: 15611432]

Cork 2009

Cork MJ, Danby SG, Vasilopoulos Y, Hadgraft J, Lane M,

Moustafa M, et al.Epidermal Barrier Dysfunction in Atopic

Dermatitis. Journal of Investigative Dermatology 2009;128

(9):1892–1908. [DOI: 10.1038/jid.2009.13]

Darsow 2010

Darsow U, Wollenberg A, Simon D, Taieb A, Werfel T,

Oranje A, et al.ETFAD/EADV eczema task force 2009

position paper on diagnosis and treatment of atopic

dermatitis. Journal of the European Academy of Dermatology

and Venereology : JEADV 2010;24(3):317–28. [PUBMED:

19732254]

Dirven-Meijer 2008

Dirven-Meijer PC, Glazenburg EJ, Mulder PG, Oranje AP.

Prevalence of atopic dermatitis in children younger than 4

years in a demarcated area in central Netherlands: the West

Veluwe Study Group. The British Journal of Dermatology

2008; Vol. 158, issue 4:846–7.

Flohr 2004

Flohr C, Johansson SG, Wahlgren CF, Williams H. How

atopic is atopic dermatitis?. The Journal of Allergy and

Clinical Immunology 2004;114(1):150–8. [PUBMED:

15241359]

Grimalt 2007

Grimalt R, Mengeaud V, Cambazard F. The steroid-

sparing effect of an emollient therapy in infants with atopic

dermatitis: a randomized controlled study. Dermatology

2007;214(1):61–7. [PUBMED: 17191050]

Hanifin 1980

Hanifin JM, Rajka G. Diagnostic features of atopic

dermatitis. Acta Dermato Venereologica 1980;59(Suppl 92):

44–7.

Hanifin 2001

Hanifin JM, Thurston M, Omoto M, Cherill R, Tofte

SJ, Graeber M. The eczema area and severity index

(EASI): assessment of reliability in atopic dermatitis. EASI

Evaluator Group. Experimental Dermatology 2001;10(1):

11–8. [PUBMED: 11168575]

Higgins 2011

Higgins JPT, Green S (editors). Cochrane Handbook

for Systematic Reviews of Interventions. Version 5.1.0

[updated March 2011]. The Cochrane Collaboration.

available from www.cochrane-handbook.org.

Johansson 2001

Johansson SG, Hourihane JO, Bousquet J, Bruijnzeel-

Koomen C, Dreborg S, Haahtela T, et al.A revised

nomenclature for allergy. An EAACI position statement

from the EAACI nomenclature task force. Allergy 2001;56

(9):813–24. [PUBMED: 11551246]

Johansson 2004

Johansson SG, Bieber T, Dahl R, Friedmann PS, Lanier

BQ, Lockey RF, et al.Revised nomenclature for allergy for

global use: Report of the Nomenclature Review Committee

of the World Allergy Organization, October 2003. The

Journal of Allergy and Clinical Immunology 2004;113(5):

832–6. [PUBMED: 15131563]

Kunz 1997

Kunz B, Oranje AP, Labreze L, Stalder JF, Ring J, Taieb A.

Clinical validation and guidelines for the SCORAD index:

consensus report of the European Task Force on Atopic

Dermatitis. Dermatology 1997;195(1):10–9. [PUBMED:

9267730]

Langan 2006

Langan SM, Thomas KS, Williams HC. What is meant

by a “flare” in atopic dermatitis? A systematic review and

proposal. Archives of Dermatology 2006;142(9):1190–6.

[PUBMED: 16983006]

Lawson 1998

Lawson V, Lewis-Jones MS, Finlay AY, Reid P, Owens

RG. The family impact of childhood atopic dermatitis:

the Dermatitis Family Impact Questionnaire. The British

Journal of Dermatology 1998;138(1):107–13. [PUBMED:

9536231]

Lewis-Jones 1995

Lewis-Jones MS, Finlay AY. The Children’s Dermatology

Life Quality Index (CDLQI): initial validation and practical

use. The British Journal of Dermatology 1995;132(6):942–9.

[PUBMED: 7662573]

Lewis-Jones 2001

Lewis-Jones MS, Finlay AY, Dykes PJ. The Infants’

Dermatitis Quality of Life Index. The British Journal of


Lewis-Jones 2007

Lewis-Jones S, Mugglestone MA, Guideline Development

Group. Management of atopic eczema in children aged up

to 12 years: summary of NICE guidance. BMJ 2007;335

(7632):1263-4. [PUBMED: 18079551]

Nice CG57 2007

National Institute for Health and Clinical Excellence

(Nice). Atopic eczema in children. Management of atopic

eczema in children from birth up to the age of 12. CG57.

National Collaborating Centre for Women’s and Children’s

Health. Commissioned by the National Institute for Health

and Clinical Excellence 2007.

Oranje 2007

Oranje AP, Glazenburg EJ, Wolkerstorfer A, de Waard-van

der Spek FB. Practical issues on interpretation of scoring

atopic dermatitis: the SCORAD index, objective SCORAD

and the three-item severity score. The British Journal of


Oranje 2010

Oranje AP, de Waard-van der Spek FB, Ordonez C, De

Raeve L, Spierings M, van der Wouden JC. Emollients for

eczema. Cochrane Database of Systematic Reviews 2010, Issue

1. [DOI: 10.1002/14651858.CD008304]



Smith 2010

Smith SD, Hong E, Fearns S, Blaszczynski A, Fischer

G. Corticosteroid phobia and other confounders in the

treatment of childhood atopic dermatitis explored using

parent focus groups. Australasian Journal of Dermatology

2010;51(3):168–74. [PUBMED: 20695854]

Sugimoto 2007

Sugimoto M, Arai I, Futaki N, Honma Y, Sakurai T,

Hashimoto Y, et al.Putative mechanism of the itch-scratch

circle: repeated scratching decreases the cutaneous level

of prostaglandin D2, a mediator that inhibits itching.

Prostaglandins, Leukotrienes, and Essential Fatty Acids 2007;

76(2):93–101. [PUBMED: 17250998]

Traidl-Hoffmann 2010

Traidl-Hoffmann C, Mempel M, Beloni B, Ring J,

Schnopp C. Therapeutic management of atopic eczema.

Current Drug Metabolism 2010;11(3):234–41. [PUBMED:

20406188]

Whalley 2004

Whalley D, McKenna SP, Dewar AL, Erdman RA,

Kohlmann T, Niero M, et al.A new instrument for

assessing quality of life in atopic dermatitis: international

development of the Quality of Life Index for Atopic

Dermatitis (QoLIAD). The British Journal of Dermatology

2004;150(2):274–83. [PUBMED: 14996098]

Willemsen 2009

Willemsen MG, van Valburg RW, Dirven-Meijer PC,

Oranje AP, van der Wouden JC, Moed H. Determining

the severity of atopic dermatitis in children presenting in

general practice: an easy and fast method. Dermatology

Research and Practice 2009;2009:357046. [DOI: 10.1155/

2009/357046; PUBMED: 20585477]

Williams 1994

Williams HC, Burney PG, Hay RJ, Archer CB, Shipley

MJ, Hunter JJ, et al.The U.K. Working Party’s Diagnostic

Criteria for Atopic Dermatitis. I. Derivation of a minimum

set of discriminators for atopic dermatitis. The British

Journal of Dermatology 1994;131(3):383–96. [PUBMED:

7918015]

Williams 2008

Williams H, Stewart A, von Mutius E, Cookson W,

Anderson HR. Is eczema really on the increase worldwide?.

The Journal of Allergy and Clinical Immunology 2008;121

(4):947–54.e15. [PUBMED: 18155278]

Wolkerstorfer 1999

Wolkerstorfer A, de Waard van der Spek FB, Glazenburg

EJ, Mulder PG, Oranje AP. Scoring the severity of atopic

dermatitis: three item severity score as a rough system for

daily practice and as a pre-screening tool for studies. Acta

Dermato-Venereologica 1999;79(5):356–9. [PUBMED:

10494710]∗ Indicates the major publication for the study

A P P E N D I C E S

Appendix 1. Draft Medline (OVID) search strategy

1. exp Eczema/ or eczema.ti,ab.

2. exp Dermatitis, Atopic/

3. neurodermatitis.ti,ab. or exp Neurodermatitis/

4. exp Dermatitis/ or dermatitis.ti,ab.

5. or/1-4

6. topical corticosteroid$.ti,ab.

7. topical steroid$.ti,ab.

8. exp Clobetasol/

9. (clobetasol or temovate or diprolene or psorocon or ultravate).ti,ab.

10. exp Betamethasone/

11. (betamethasone or diflorasone or halobetasol).ti,ab.

12. exp Triamcinolone/

13. exp Halcinonide/

14. exp Fluocinonide/

15. exp Desoximetasone/

16. (amcinonide or mometasone or halcinonide or fluocinonide or desoximetasone).ti,ab.

17. (cyclocort or diprolene or diprosone or elocon or florone or halog or lidex or maxiflor or psorcon or topicort).ti,ab.

18. (fluticasone or aristocort or cutivate or valisone).ti,ab.



19. exp Fluocinolone Acetonide/

20. (locoid or westcort).ti,ab.

21. (hydrocortisone or fluocinolone or fluranodrenolide or cordran or kenalog or synalar).ti,ab.

22. exp Flumethasone/

23. exp Desonide/

24. (alcometasone or flumethasone or desonide or aclovate or locorten or tridesilon or valisone).ti,ab.

25. (eumovate or clobetasone butyrate).ti,ab.

26. exp Adrenal Cortex Hormones/

27. or/6-26

28. randomized controlled trial.pt.

29. controlled clinical trial.pt.

30. randomised.ab.

31. placebo.ab.

32. clinical trials as topic.sh.

33. randomly.ab.

34. trial.ti.

35. 28 or 29 or 30 or 31 or 32 or 33 or 34

36. exp animals/ not humans.sh.

37. 35 not 36

38. 5 and 27 and 37

H I S T O R Y

Protocol first published: Issue 10, 2012

C O N T R I B U T I O N S O F A U T H O R S

HM was the contact person with the editorial base.

HM co-ordinated the contributions from the co-authors and wrote the final draft of the protocol.

HM and JCvdW worked on the methods sections.

HM, QY, APO, and SP drafted the clinical sections of the background and responded to the clinical comments of the referees.

HM and JCvdW responded to the methodology and statistics comments of the referees.

All authors contributed to writing the protocol.

HM is the guarantor of the final review.

D E C L A R A T I O N S O F I N T E R E S T

Professor Arnold Pieter Oranje has conducted several fluticasone propionate studies, and, currently, he is conducting a wet wrap study

with diluted mometasone furoate ointment. He is also involved in a fluticasone propionate study.

The clinical referee, Dr Phyllis Spuls, designed and performed a study (in 1995) relating to this subject, which has not been published:

’Pulse versus continuous topical corticosteroids in atopic dermatitis in children’. She has written a prefinal version of the manuscript.



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