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.