'Mind and Skin': A prospective cohort study evaluating the impact of inflammation, itch and sleep disturbance on the brain, mental health and cognition, in patients with severe atopy.

Atopic eczema is an intensely itchy skin disease which often starts in infancy or early childhood. It can have profound effects on patients' quality of life and cause long-lasting psychological impairment. Sleep may be very disturbed. More severe disease often requires oral/injectable immuno-modulatory treatments (i.e. medications which control symptoms by influencing the immune system).

There is an association between eczema, impaired cognitive functioning and mental health disorders, but the underlying mechanisms are not clearly defined.

This projects examines the links between inflammation-driven itching and disturbed sleep, and how this might be causally responsible for systemic and brain inflammation, disturbance of cognitive functioning and mental health problems. The investigators will also study potential changes occurring following an improvement in eczema when patients are treated with systemic immuno-modulators.

Key investigations will include:

i) Home-based sleep studies using a commercially available sleep devices (for example DREEM headband, Philips Actiwatch, oximetry) ii) Structural and functional magnetic resonance imaging (MRI) of the brain, iii) Blood tests to quantify systemic inflammation iv) Genetic analyses, particularly related to the immune system, circadian rhythm (the "internal 24-hour clock"), skin barrier function and the risk of developing eczema or associated diseases, v) Assessments of the skin's barrier function vi) Stool samples and skin swabs to study the gut and skin microbiome.

The investigators will utilise existing anonymised data for comparative purposes (e.g. from patients with Attention Deficit Hyperactivity Disorder (ADHD) and healthy controls who previously had brain imaging.)

The investigators will explore eczema patients' and families' perception of their disease, in particular itch and the resulting sleep loss, through focus groups, to better understand the sociological impact of eczema, and how these patients' interactions with the external world and society are affected by eczema. Importantly, this will include exploration of family dynamics, as patients with eczema often have profound sleep disturbance from early life, which can impact on their caregivers' sleep and quality of life.

Inclusion Criteria:

1. Patients aged 12 to 18 with atopic eczema (groups 1 and 2), which has been diagnosed by a Consultant Dermatologist.
2. Patients with atopic eczema warranting systemic immuno-modulatory therapy or patients with atopic eczema on topical therapy or healthy controls.
3. Written informed consent for study participation obtained from the patient or from the parent(s) / legal guardian, with assent as determined by the patient's age and level of understanding.
4. Willingness to comply with all study requirements.
5. Competent use of English language, according to patient's age (patients will be required to understand the written questionnaires and complying with instructions during MRI scanning).

Exclusion Criteria:

1. Insufficient understanding of the study by the patient and/or parent/guardian.
2. Any clear contra-indication to MRI scanning. In particular this would be due to the presence of any implanted devices or metal from previous surgery or accident. This would be fully assessed with a standardised safety questionnaire by a radiographer prior to MRI scanning.
3. Any condition deemed by the Investigator to limit a patient's ability to undertake MRI components of the study, for example significant claustrophobia.
4. Diagnosed by a sleep medicine specialist with a formal sleep disorder, requiring systemic medication.
5. Sleep disturbance from co-morbid illness (including physical and/or mental/psychological illness) other than atopic eczema, deemed by the Investigator to significantly impact on sleep components of the study.
6. Previous and/or current substance misuse.
7. Patients who take medications that would, in the investigator's opinion, impact on quality of sleep studies.

Group 1: Patients aged 12-18 who have been diagnosed with eczema and require systemic therapy.

Group 2: Patients aged 12-18 who have been diagnosed with eczema and require topical therapy only.

Group 3: Patients aged 12-18 who do not have eczema.