Centre of Evidence Based Dermatology

What is meant by 'flare' in atopic dermatitis?

Flare Definitions

A ‘flare’ or ‘flare up’ is a term commonly used in both scientific and non-scientific literature to refer to a disease exacerbation. Being able to capture flares may assist with assessing the long-term control of a disease. As flares are usually defined by the patient based on their personal experience, their assessment within the context of a clinical trial requires some degree of standardization (Langan et al 2006).   

Our 2014 literature review (Langan et al 2014) identified a large range of flare definitions in-use within clinical studies, based on arbitrary cut-offs, behavioural changes, symptoms and those evaluating more than one of these factors (composite definitions). Furthermore, none of the identified definitions had been validated.    

To address this issue, we performed a validation study (Thomas et al 2015) evaluating treatment escalation as a flare definition for eczema. We found that 'escalation of treatment' was a good measure of eczema flares, but a simpler approach may be to simply collect 'use of topical anti-inflammatory medications,' which appeared to be just as good as escalation of treatment, but is potentially simpler to collect. The study suggested that daily recording of medication use was feasible and appeared to be a good indicator of long-term control.    

Many of the practical issues inherent in the measurement of eczema flares, in clinical trials have still to be addressed. This work is being driven by the Long-term Control Working Group for the Harmonizing Outcome Measures for Eczema (HOME) Initiative.

Totally and well controlled weeks (TCW and WCW)

As a disease model, asthma has many similarities with eczema and the work of the Global Initiatives for Asthma / National Institutes of Health guidelines provides a useful model to follow. We propose that the concepts of totally controlled weeks (TCW) and well controlled weeks (WCW) should be considered for adoption in eczema research and some simple definitions PDF format have been outlined here.  

These definitions provide an intuitive means of assessing long-term disease control and are appropriate for use in a variety of clinical trial settings, as well as for epidemiological research.

Using these definitions, a TCW is one in which no rescue treatment has been applied and in which symptoms are well controlled every day. Rescue treatment is defined as any treatment (other than emollient) that is applied in response to a worsening of the disease. Within the confines of a clinical trial, this would usually be “rescue treatment” as defined by the study protocol, but could also be the study treatment itself if it is applied in response to changes in disease activity.

A WCW is one in which treatment has been applied for a period of less than or equal to 2 days and symptoms are controlled most of the time. These definitions are based on assessments over consecutive seven day periods.

Choosing treatment, symptoms and duration as the components of these definitions, rather than signs, is pragmatically chosen to suit clinical research where daily or weekly patient review is often impractical.

WCWs have been demonstrated to be valid and feasible for measuring long-term control in atopic dermatitis trials (Langan et. al 2017). However, ceiling effects and burden of data collection can limit use.

When is it appropriate to use these tools?

Including well controlled weeks or flares as an outcome measure is not always useful in clinical trials. It is important to strike a balance between capturing meaningful outcomes that are understood by patients and clinicians (such as well controlled weeks or flares) and using outcomes that are sufficiently sensitive to capture a difference in treatment response.

In order to inform this decision processPDF format, a possible decision pathway has been outlined. 

This was a retrospective review of studies which were not primarily devised to define flares of eczema. Our recommendations therefore require validation in clinical studies


What is Meant by a “Flare” in Atopic Dermatitis?
Langan et al. (2006) Arch Dermatol;142(9):1190-6.

How are eczema ‘flares’ defined? A systematic review and recommendation for future studies 
Langan et al. (2014) British Journal of Dermatology; 170, pp548–556

Validation of treatment escalation as a definition of atopic eczema flares
Thomas et al. (2015) PLoS One; 21;10(4):e0124770.

Measuring long-term disease control in patients with atopic dermatitis: A validation study of well-controlled weeks
Langan et al. (2017) J Allergy Clin Immun

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