Itching for innovation: role of aryl hydrocarbon receptor agonists as a future therapy for atopic dermatitis.

Atopic dermatitis (AD) is a chronic, inflammatory skin condition which affects over 200 million people worldwide, with patients commonly presenting with dry, itchy and sore skin. The challenge in finding optimal treatment for AD stems from the heterogenous nature of the disease and its multifaceted aetiology: skin barrier dysfunction, immune system dysregulation, genetic factors, environmental factors and alterations in skin microorganisms. Traditional treatments for AD such as corticosteroids, calcineurin inhibitors and immunosuppressants have several limitations such as reoccurrence of symptoms when discontinued, lack of targeted action and risk of adverse effects.

Erosive lichen planus: an unmet disease burden.

Objectives: To explore the demographic and clinical profile of erosive lichen planus (ELP) across multiple ethnicities within a single cohort, deepening our understanding of disease severity, progression and outcomes.

Methods: A longitudinal retrospective cohort study of ELP patients in the ethnically diverse population of East London was carried out, profiling ELP ( = 57) against the milder reticular lichen planus (RLP) ( = 35).

Results: A higher prevalence of ELP was observed in white populations compared to other ethnicities.

Upregulation of keratin 15 is required for varicella-zoster virus replication in keratinocytes and is attenuated in the live attenuated vOka vaccine strain.

Varicella-zoster virus (VZV) is the etiological agent of chickenpox and shingles, diseases characterised by epidermal virus replication in skin and mucosa and the formation of blisters. We have previously shown that VZV infection has a profound effect on keratinocyte differentiation, altering the normal pattern of epidermal gene expression. In particular, VZV infection reduces expression of suprabasal keratins 1 and 10 and desmosomal proteins, disrupting epidermal structure to promote expression of a blistering phenotype.

Vitamin D deficiency and atopic dermatitis severity in a Bangladeshi population living in East London: A cross-sectional study.

Background: Atopic eczema is a common, chronic, inflammatory skin condition with considerable heterogeneity. South Asian people living in the UK frequently have low serum vitamin D3 (25(OH)D), and those with atopic disease can present with severe eczema. The association between vitamin D deficiency and eczema severity, and the role of vitamin D supplementation in atopic eczema is inconsistent, and under-researched in people with Asian ancestry.

Loss-of-function FLG mutations are associated with reduced history of acne vulgaris in a cohort of patients with atopic eczema of Bangladeshi ancestry in East London.

Background: Acne vulgaris (AV) is the eighth most common nonfatal disease globally. Previous work identified an association between AV and increased filaggrin (FLG) protein expression in the follicular epidermis, but further work did not find a clear link between loss-of-function (LoF) FLG gene mutations and protection from AV.

Objectives: To explore any association between AV and FLG LoF mutations in a cohort of genotyped patients of Bangladeshi ancestry with atopic eczema (AE) in East London.

Rare disease gene association discovery from burden analysis of the 100,000 Genomes Project data.

To discover rare disease-gene associations, we developed a gene burden analytical framework and applied it to rare, protein-coding variants from whole genome sequencing of 35,008 cases with rare diseases and their family members recruited to the 100,000 Genomes Project (100KGP). Following triaging of the results, 88 novel associations were identified including 38 with existing experimental evidence. We have published the confirmation of one of these associations, hereditary ataxia with , and independent confirmatory evidence has recently been published for four more.

Ichthyosis linked to sphingosine 1-phosphate lyase insufficiency is due to aberrant sphingolipid and calcium regulation.

Sphingosine 1-phosphate lyase (SGPL1) insufficiency (SPLIS) is a syndrome which presents with adrenal insufficiency, steroid-resistant nephrotic syndrome, hypothyroidism, neurological disease, and ichthyosis. Where a skin phenotype is reported, 94% had abnormalities such as ichthyosis, acanthosis, and hyperpigmentation. To elucidate the disease mechanism and the role SGPL1 plays in the skin barrier we established clustered regularly interspaced short palindromic repeats-Cas9 SGPL1 KO and a lentiviral-induced SGPL1 overexpression (OE) in telomerase reverse-transcriptase immortalised human keratinocytes (N/TERT-1) and thereafter organotypic skin equivalents.