J. Bandier

Skin reaction and regeneration after single sodium lauryl sulfate exposure stratified by filaggrin genotype and atopic dermatitis phenotype

Filaggrin is key for the integrity of the stratum corneum. Mutations in the filaggrin gene (FLGnull) play a prominent role in atopic dermatitis (AD) pathogenesis. People with AD have increased susceptibility to irritants. However, little is known about the effect of filaggrin genotype and AD phenotype on irritant response and skin regeneration.

Carriers of filaggrin gene (FLG) mutations avoid professional exposure to irritants in adulthood

Loss‐of‐function mutations in the filaggrin gene (FLG) are associated with xerosis, atopic dermatitis, and early onset of hand eczema. Irritant exposure is a risk factor for occupational hand eczema, and FLG mutations increase the risk of occupational irritant contact dermatitis on the hands in hospital cohorts. It is unknown whether FLG mutations affect the level of irritant exposure.

The role of the skin microbiome in atopic dermatitis: a systematic review†

Dysbiosis is a hallmark of atopic dermatitis (AD). The composition of skin microbiome communities and the causality of dysbiosis in eczema have not been well established. The objective of this review is to describe the skin microbiome profile in AD and address whether there is a causal relationship between dysbiosis and AD. The protocol is registered in PROSPERO (CRD42016035813). We searched PubMed, Embase, Scopus and ClinicalTrials.gov for primary research studies applying culture‐independent analysis on the microbiome on AD skin of humans and animal models. Two authors independently screened the full text of studies for eligibility and assessed risk of bias. Because of heterogeneity no quantitative synthesis was done. Of 5735 texts, 32 met the inclusion criteria (17 published: 11 human and six animal studies). The studies varied in quality and applied different methodology. The skin in AD had low bacterial diversity (lowest at dermatitis‐involved sites) and three studies showed depletion of Malassezia spp. and high non‐Malassezia fungal diversity. The relative abundance of Staphylococcus aureus and Staphylococcus epidermidis were elevated and other genera were reduced, including Propionibacterium. A mouse study indicated that dysbiosis is a driving factor in eczema pathogenesis. The data are not sufficiently robust for good characterization; however, dysbiosis in AD not only implicates Staphylococcus spp., but also microbes such as Propionibacterium and Malassezia. A causal role of dysbiosis in eczema in mice should encourage future studies to investigate if this also applies to humans. Other important aspects are temporal dynamics and the influence of methodology on microbiome data.

Epidermal filaggrin deficiency mediates increased systemic T-helper 17 immune response.

Cellular T‐helper (Th)17 infiltrates dominate skin inflammation in filaggrin‐deficient flaky tail (ft/ft) mice, and Th17 cells are found in both the skin and blood of patients with acute atopic dermatitis. However, the potential role of loss‐of‐function mutations in the filaggrin gene (FLG) for increased peripheral Th17 cells is unclear.

Individuals with complete filaggrin deficiency may have an increased risk of squamous cell carcinoma

patients with chronic plaque psoriasis. Br J Dermatol 2012; 166:505–10. 5 Field S, Newton-Bishop JA. Melanoma and vitamin D. Mol Oncol 2011; 5:197–214. 6 Waldron JL, Ashby HL, Cornes MP et al. Vitamin D: a negative acute phase reactant. J Clin Pathol 2013; 66:620–2. 7 Shee C. Is hypovitaminosis D a consequence rather than cause of disease? Thorax 2013; 68:679. 8 Autier P, Boniol M, Pizot C, Mullie P. Vitamin D status and ill health: a systematic review. Lancet Diabetes Endocrinol 2014; 2:76–89. 9 Bouillon R, Van Shoor NM, Gielen E et al. Optimal vitamin D status: a critical analysis on the basis of evidence-based medicine. J Clin Endocrinol Metab 2013; 98:E1283–304. 10 Cashman KD, Muldowney S, McNulty B et al. Vitamin D status of Irish adults: findings from the National Adult Nutrition Survey. Br J Nutrition 2013; 109:1248–56.

Skin pH, Atopic Dermatitis, and Filaggrin Mutations

BackgroundThe acidic pH of the skin plays a role in antimicrobial defense by regulating the bacterial skin flora and aspects of barrier. Filaggrin is a co-factor in maintaining a low skin pH because of its degradation into acidic amino acids. Accordingly, lack of filaggrin due to filaggrin mutations may influence skin pH. ObjectiveWe aimed to determine the epidermal pH in different groups stratified by filaggrin mutations and atopic dermatitis. Further, we investigated the changes in pH according to severity of mutational status among patients with dermatitis, irrespective of skin condition. MethodspH was measured with a multiprobe system pH probe (PH 905), and the study population was composed of 67 individuals, who had all been genotyped for 3 filaggrin mutations (R501X, 2282del4, R2447X). ResultsWe found no clear pattern in relation to filaggrin mutation carrier status. Individuals with wild-type filaggrin displayed both the most acidic and most alkaline values independent of concomitant skin disease; however, no statistical differences between the groups were found. ConclusionsThe lack of significant diversity in skin pH in relation to filaggrin mutation carrier status suggests that the effect of filaggrin mutations on skin pH is not pronounced.

Contact allergy to methyldibromo glutaronitrile is still of clinical relevance: METHYLDIBROMO GLUTARONITRILE ALLERGY

The prevalence of contact allergy to the preservative methyldibromo glutaronitrile (MDBGN) has decreased dramatically since its use in leave-on and rinse-off cosmetics was prohibited in EU member states in 2005 and 2008, respectively (1). Importantly, current clinical relevance of positive patch test reactions has almost disappeared in Denmark (2). Here, we present 2 cases of allergic contact dermatitis caused by exposure to MDBGN in a cleaning detergent and sunscreen agent, respectively, showing that positive patch test reactions to MDBGN can, indeed, still be of current clinical relevance, and that possible exposures should be investigated.

Skin prick test reactivity to aeroallergens by filaggrin mutation status

Background  Studies have shown that filaggrin gene (FLG) mutations are positively associated with sensitization to aero allergens. We hypothesized that FLG mutations would also have an effect on the mean size of positive skin prick test (SPT) reactions as well as the number of positive reactions.

Concentration of filaggrin monomers, its metabolites and corneocyte surface texture in individuals with a history of atopic dermatitis and controls

Atopic dermatitis (AD) is characterized by skin barrier dysfunction. Notably, a high number of nano‐scale protrusions on the surface of corneocytes, which can be expressed by the Dermal Texture Index (DTI), were recently associated with paediatric AD, loss‐of‐function mutations in filaggrin gene (FLG) and reduced levels of natural moisturizing factors (NMF). No study has so far examined the association between these parameters and monomeric filaggrin levels in adults.

Information about filaggrin genotype is valuable for adult atopic dermatitis patients.

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