Characterisation of Skin Microstructure Under Normal and Atrophied States

Around 24% of the United Kingdom (UK) population seeks medical attention regarding a skin condition each year, of which 6.1% are referred to specialist dermatology care. Skin conditions are the most common reason for people to consult their General Practitioner (GP) (average of 630 consultations per GP every year). The most common skin conditions include eczema, psoriasis, acne, rosacea and urticaria. All are chronic inflammatory conditions with complex aetiology that require regular treatment (there is no cure). Each of these conditions has a significant impact on quality of life, with that impact being similar to epilepsy, asthma, cystic fibrosis, and renal disease for eczema, urticaria and psoriasis. Beyond new treatments, new ways of characterising these conditions are needed to better inform treatment decisions (treatment choice and regimen) and improve long-term management.

Recent research has demonstrated the potential of OCT to visually characterise skin inflammation. Conceptually similar to ultrasound, OCT uses light instead of sound to generate volumetric scans of the skin. With an axial resolution of <5 µm and a penetration depth of <2mm, cross-sectional images of the skin are comparable to tissue sections obtained via biopsy. In addition to enabling the quantification of the structural features of the skin, further processing can be used to derive detailed angiographs of the superficial dermal vasculature and birefringence patterns associated with dermal collagen structure. Several interesting metrics can be derived from OCT images, including epidermal thickness, depth of the superficial plexus, diameter of blood vessels, density of the vascular network, and index of collagen matrix. Through the investigating team's work on the Skin Pathology assessment with Optical Technologies (SPOT) study, a strong association between OCT-derived metrics like this and disease severity at specific anatomical locations (the cubital fossae) has been revealed in Atopic dermatitis (AD) patients. These metrics can be used to objectively assess the severity of eczema. In addition to enabling rapid and non-invasive monitoring of treatment efficacy (normalisation of skin structure) over time, they can also be used to quantify the adverse effects of inappropriate or excessive treatment. For example, the investigators have previously shown that continued use of topical corticosteroids (TCS) over short periods (4 weeks) in clinically clear appearing skin leads to marked epidermal thinning, altered vasculature, and disrupted collagen structure. A recent review provides a comprehensive appraisal of clinical data relating to several inflammatory skin conditions and the skin atrophy induced from long-term treatment with TCS. The report suggests a relationship between the dose, frequency, duration and anatomical area of application of TCS with the degree of atrophy, and proposes that clinically relevant skin atrophy is more likely to occur from chronic long-term (including intermittent) use of TCS rather than short-term reactive use. Subclinical changes may mark the progression toward clinical adverse effects of TCS misuse, including for example, striae and telangiectasia. Further characterisation of these clinically significant skin changes by OCT is required to inform the understanding of the scale of changes in skin microstructure required to yield clinically significant effects. To do this, researchers also need a robust understanding of healthy skin microstructure.

There are a number of adverse effects associated with TCS use, where used inappropriately or excessively. These adverse effects include hypopigmentation, hypertrichosis, telangiectasia, infection, perioral dermatitis, and atrophy. Usually, these adverse effects are thought to be reversible, but excessive skin atrophy can induce striae atrophicae, which is irreversible. Rarely, systemic absorption can occur due to excessive or long-term use of high-potency TCS, affecting the hypothalamic-pituitary adrenal axis response. However, the risks of TCS-induced Adverse events (AE) can be minimised by using the right dose for limited periods of time (measured in weeks). Epidermal thickness appears to return to normal values within a few weeks after stopping TCS treatment. Parents and carers of AD patients can develop steroid phobia from TCS adverse effects due misinformation from the internet, social media and mixed messages delivered by medical professionals such as GPs, pharmacists or dermatologists who have left clinical practice. This places a significant burden on healthcare workers and caregivers due to underutilisation of TCS, resulting in uncontrolled AD with multiple flare-ups that may require systemic treatment. Further research into the conditions of TCS AEs is required to clarify confusion about their use and enable healthcare professionals (HCPs) to both optimise their safe use and alay patient fears. It is important to educate and train the patient on how to apply the right amount of TCS with the right frequency for each part of the body. Because TCS vary in potency, their safety profiles vary too. According to the British National Formulary (BNF) all topical corticosteroids share side-effects of which some are common or very common (skin reactions, telangiectasia), rare or very rare (adrenal suppression, hypertension, skin depigmentation; may be reversible), and some have unknown frequencies (local reaction, vasodilation). In addition to the major side-effects common to all TCS there are more specific ones for each class and product.

Psychological stress has been shown to exert negative effects on the skin including impaired skin barrier function, loss of stratum corneum integrity and altered immunity. These effects are mediated through the stress-induced hormone cortisol (an endogenously produced steroid). This suggests that a person's stress level and associated cortisol level may be a factor in determining their resting epidermal structure. In fact, the atrophic effects of topically applied corticosteroids (synthetic cortisol derivatives) on the skin demonstrates clearly the impact of glucocorticoid receptor activation on epidermal structure. Moreover, stress, resulting in elevated cortisol levels and Hypothalamic-Pituitary-Adrenal (HPA) -axis overactivation is a recognised trigger for atopic dermatitis and contributes to its progression. Given that, the investigators seek to both understand variations in healthy skin structure and the effects of long-term corticosteroid use, understanding the contribution of stress and the body's cortisol level are important factors. Here the investigators will measure cortisol awakening response from saliva and assess participants stress levels using validated scales.