AIM: To identify factors that predict persistent atopic eczema and/or negative psychological outcomes in children with atopic eczema.

BACKGROUND: Atopic eczema (AE, otherwise known as atopic dermatitis) is one of the commonest disorders in childhood. The disease is characterized by generalized dry skin, pruritis, and typically flexural erythema. Symptoms usually start before two years of age, and in the UK, most children will be diagnosed and treated by their general practitioner. Whilst the majority of children will have mild symptoms that improve as they get older, a significant proportion of those affected will have more severe and persistent eczema.

Our knowledge about the natural history of AE and factors that might predict persistence beyond the pre-school years is limited by the methodological imperfections of research conducted to date. Most studies have either been small, retrospective case series; suffered from a short duration of follow-up; or recruited participants from hospital in or out-patients.1 As a consequence the findings may be unrepresentative of children in the community and subject to the many biases that are associated with a retrospective study design. The only two significant cohort studies are by Williams and Strachan2 and Illi.3 Early onset of disease, severity, atopic sensitization and a strong atopic family history were associated with a worse prognosis.

As well as the physical burden of the disease, a series of studies have suggested AE can have a significant psychological impact as well. However, nearly all of these studies have serious limitations of one form or another, related to size of the study, the population from which their sample was drawn (mainly hospital out-patients), the design of the study (most are cross-sectional) and/or the outcome examined (the majority examine the psychological effect of AE on the child only). Only one recently published study by Schmitt et al4 followed-up a sizeable cohort of children for a reasonable length of time. It reported that children with infant-onset eczema were more likely to have emotional disturbance, but data on psychological health were collected just at one time-point (age 10 years) and only on the affected child.

This project will build on earlier research that has examined children in ALSPAC who have AE5-8 and address many of the limitations of previous studies that have examined prognostic factors and the psychological consequences of AE. Specifically, participants in ALSPAC were recruited from the community rather than specialist care settings; relevant data has been collected prospectively from several sources (parent, school and physical examination) with good rates of follow-up; data are available into adolescence and beyond; and clear definitions of AE can be applied using previously described criteria.5,6 For the first time will we link data available on both child and parental mental health to persistent eczema, to assess the impact of AE on both the child and the family.

In addition to answering the research questions posed, one of the outputs from this project will be to produce a map all of the questions relevant to AE. Serial questionnaires are the main source of data in ALSPAC and a detailed manual identifies which psychological instruments and have been used when. Unfortunately there in no comparable document that describes the all the different questions relating to AE. By comprehensively documenting for the first time the method of collection, timing and nature of data on AE, a valuable resource will be made available to future researchers wanting to interrogate ALSPAC for studies of AE.

Finally, we will extend the analysis performed by Wadonda-Kabondo et al5 on the prevalence and incidence of AE between to include children up to 128 months old.

PLAN OF INVESTIGATION:

We will examine data on data on parents and children both antenatal and up to 12 years of age. We have chosen this upper age limit because it is a natural watershed between childhood and early adolescence; it fits with age range of the 2007 NICE guidance; and because it represents a significant amount of data that can be explored, with potential for important findings, within the proposed research timeframe and budget. Also, previous work suggests that after the age of 11 years, the proportion of children whose eczema persists is relatively constant.2 However, once the methods have been established, dependent of course upon the findings of this study and subject to application for further funding, the approach applied to the 0-12 year age group could of course be extended to look at the 13-18 year age group and upwards.

Definition of AE: We will adopt the case of definition of AE used by Wadonda-Kabondo et al:5,6 children with a reported rash on at least two separate occasions. This was found to give estimates of the prevalence and cumulative incidence of AE similar to those from other studies.9,10 We will further sub-divide children with AE into three groups on the basis of whether AE is reported before or after 2 years of age: infant onset clearing (present before age 2 years but not after), infant onset persistent (present before age 2 years and after), or late onset (present after age 2 years but not before). Similar categories have been adopted by Illi et al3 and Schmitt et al4 and permits analysis of data and reporting of these sub-groups in a way that is reflects the patterns of AE clinicians commonly see.

Psychological measures: The psychological health of the child will be assessed using the Strength and Difficulties Questionnaire (SDQ),11 which was completed by parents at 4, 7, 8 and 11 years and the child's school at 8 and 10 years. SDQ scores above the 90th centile indicate problem behaviours and are associated with a substantially increased risk of psychiatric disorder.11 Parental psychological (depression and anxiety) health will be assessed using the Edinburgh Post-Natal Depression Score (EPDS)12 and the anxiety items from Crown-Crisp Experiential Index (CCEI).13 Mothers and father complete EPDS and CCEI approximately annually up to 11 years of age.

Analysis: 1) All of the questionnaires will be reviewed for questions pertaining AE and previously described risk factors for onset and persistence of AE. Undertaking this preliminary work will be important to both this study but also in establishing a map of atopy and skin questions in the ALSPAC dataset that will be of use in future ALSPAC-based research of AE. 2) Based on parental report, we will calculate and report the incidence and prevalence of AE at different time-points. We will also examine the reliability of the reporting of eczema. First, by comparing responses to items in earlier questionnaires that ask about skin rashes with later data that asks about "ever diagnosis" of eczema. Second, by comparing reported prevalence of AE with that recorded at clinic examination. In doing this, we will extend the analysis performed by Wadonda-Kabondo and colleagues.5 3) Using the definitions of AE given above, using simple descriptive statistics we will describe the different groups of children with and without AE. Next will we examine the data for associations between AE and characteristics which may be risk factors for AE, including birth weight, gestational age, breast-feeding, early age of onset, flexural site at disease onset, female sex, allergy (peanut, egg, fish or dust mite), hay fever or asthma, social class, family size, and family history of atopy. 4) The prevalence of child and parental psychological distress at different time-points will be reported. We will compare psychological measures for children with and without AE, adjusting for known confounders; and compare psychological measures for parents (mother and partner if available) of children with and without AE, adjusting for known confounders. These analyses will be repeated for the different sub-types of AE described. Sensitivity analyses will be conducted to examine the influence of missing data on the findings

DISSEMINATION OF FINDINGS:

A final report will be sent to the British Skin Foundation and other interested professional and patient representative bodies, including the National Institute of Health and Clinical Excellence (NICE, the guideline "Atopic eczema in children" is due to be revised in 2011), relevant Royal Colleges, the University of Nottingham Centre for Evidence Based Medicine, British Association of Dermatologists, the Primary Care Dermatology Society, and the National Eczema Society. The findings will also be published in peer-reviewed scientific journals.

ABOUT THE STUDY TEAM:

Matthew Ridd is an GP and lecturer in primary care, with an interest in promoting research to understand the nature and best management of common dermatological problems seen in primary care. He will be responsible for supervising an RA who will lead on the project; monitoring budgets and progress; and producing the final report.

Sarah Purdy is a consultant senior lecturer and practicing GP. She has conducted primary research on the epidemiology and management of acne in primary care and secondary research on the management of acne and eczema in primary care. She is a clinical epidemiologist and has extensive experience of working with large datasets.

Sarah Sullivan has experience of using the ALSPAC data set, especially in relation to measures of mental health. Her PhD is using the ALSPAC cohort to examine Psychosis-like Symptoms (PLIKS) and Social Functioning.

GD is a consultant dermatologist who co-supervised Dr Wadonda-Kabondo's PhD, from which two of the most significant studies of AE using the ALSPAC dataset have been published.