Maja-Lisa Clausen

Staphylococcus aureus colonization in atopic eczema and its association with filaggrin gene mutations

Atopic dermatitis (AD) is a prevalent disease with significant impact on physical health and quality of life. Staphylococcus aureus has been directly correlated to disease severity, and may also be a contributing causal factor in the pathogenesis of AD.

Quality of life and disease severity in patients with atopic dermatitis

Atopic dermatitis (AD) affects quality of life (QoL) negatively in patients and their families. We examined the relationship between disease severity and QoL in patients with AD.

In vivo expression of antimicrobial peptides in atopic dermatitis

The aim of this review is to present findings on expression of antimicrobial peptides (AMPs) in atopic dermatitis (AD) skin, focusing only on in vivo studies, and to discuss differences in results obtained using various skin sampling techniques and different methodology for analysis of AMPs. The review also includes a discussion of the effect of frequently used treatments on AMP expression. Many studies have shown a reduced level of AMPs in lesional AD skin when compared to psoriatic skin, explaining the high frequency of AD‐related infections. Interestingly, however, non‐lesional AD skin has shown the same upregulation of AMPs after barrier disruption as non‐lesional psoriatic skin. Various methods have been used to analyse AMP expression in the skin, and when comparing these methods, differences are revealed in AMP expression depending on the method used for sampling and analysis. Comparisons indicate that analyses of mRNA levels of AMPs may find greater differences in expression than analyses of protein levels. Few studies evaluate the effect of topical treatments on the expression of AMPs, and these indicate an inhibition of AMP expression, particularly after use of corticosteroids. AMPs are important components of the skin as a defense against infections, and despite much research, the clinical importance of the effect of common treatments, including systemic treatments for AD and the interplay between AMPs and the skin microbiome, is still largely unknown.

Current knowledge on biomarkers for contact sensitization and allergic contact dermatitis

Contact sensitization is common and affects up to 20% of the general population. The clinical manifestation of contact sensitization is allergic contact dermatitis. This is a clinical expression that is sometimes difficult to distinguish from other types of dermatitis, for example irritant and atopic dermatitis. Several studies have examined the pathogenesis and severity of allergic contact dermatitis by measuring the absence or presence of various biomarkers. In this review, we provide a non‐systematic overview of biomarkers that have been studied in allergic contact dermatitis. These include genetic variations and mutations, inflammatory mediators, alarmins, proteases, immunoproteomics, lipids, natural moisturizing factors, tight junctions, and antimicrobial peptides. We conclude that, despite the enormous amount of data, convincing specific biomarkers for allergic contact dermatitis are yet to be described.

Skin Barrier Dysfunction and the Atopic March

The atopic diseases: atopic dermatitis, asthma and allergic rhinoconjunctivitis are frequent diseases in the population occurring sequentially in the young (the atopic march). The discovery of filaggrin gene (FLG) mutations and impairments in the skin barrier as predisposing factors for atopic dermatitis and subsequent asthma and atopic sensitization in the context of eczema has improved our understanding of the atopic march. The atopic diseases can now be viewed upon as causally related conditions—rather than sequentially occurring manifestations of the same underlying atopic disease state—with atopic dermatitis and FLG mutations being a prerequisite for the development of the other atopic diseases, particularly asthma. This review discusses the role of the skin barrier function, particularly the role of FLG mutations, in the atopic march.

Measurements of AMPs in stratum corneum of atopic dermatitis and healthy skin–tape stripping technique

Decreased levels of antimicrobial peptides (AMPs) in atopic dermatitis (AD) have previously been reported and have been linked to the increased susceptibility to skin infections found in AD patients. This study intents to identify AMPs: hBD-2, hBD-3, RNase7, psoriasin and LL-37 in AD patients and healthy controls, and determine concentrations in consecutive depths of the outer most skin layers. Tape stripping was used on lesional and non-lesional skin. From each skin site, 35 consecutive tape strips were collected and pooled in groups of 5. Commercially available ELISA kits were used to determine AMP concentration in stratum corneum samples. hBD-2, hBD-3, RNase7 and psoriasin were identified in stratum corneum samples. hBD-3-level was markedly higher in AD non-lesional skin compared to healthy controls, and a similar trend was observed for RNase7. Most AMPs were distributed evenly through 35 tape strips, implying a homogeneous distribution of antimicrobial defense in the outer most skin layers. The findings indicate that AD patients may not suffer from a general baseline deficiency in AMPs, and that the innate immune defense is present throughout the stratum corneum, both insights of importance for understanding the role of AMPs in AD.

The Danish Atopy Database (DAD): Rationale and Methods

Atopic dermatitis is a multifactorial chronic disease that poses a great burden for patients and society. In recent decades the prevalence has increased substantially in many countries, notably in Western societies, and the causes for this increase are not completely understood. There are still many unanswered questions regarding atopic dermatitis with re- spect to aetiology, pathophysiology, co-morbidity as well as subgrouping and treatment of the disease. Establishment of the Danish Atopy Database (DAD), a cohort with ongoing inclusion of outpatients with atopic dermatitis from a tertiary referral centre, allows the study of these aspects of the disease. Herein we present our methodological considerations in regards to establishment of this cohort.

Genomic analysis reveals different mechanisms of fusidic acid resistance in Staphylococcus aureus from Danish atopic dermatitis patients

Abstract Background Staphylococcus aureus skin colonization is common in patients with atopic dermatitis (AD) and is associated with risk of skin infections. AD patients therefore often receive antibiotic treatments, including topical treatment with fusidic acid, which have been associated with resistance development. Objectives To examine the prevalence of antibiotic resistance in S. aureus isolated from Danish AD patients, with a primary focus on fusidic acid resistance and the genetic mechanisms that underlie it. Methods One hundred and thirty-eight S. aureus isolates collected from lesional skin (n = 54), non-lesional skin (n = 27) and anterior nares (n = 57) from 71 adult AD patients were included in the study. Isolates were tested for susceptibility to 17 selected antibiotics. S. aureus whole-genome sequences were used to examine the genetic determinants of fusidic acid resistance (fusA or fusE mutations or carriage of fusB or fusC genes). Results One hundred and nine isolates (79%) were resistant to at least one of the tested antibiotics, with the most prevalent resistances being to penicillin (55%), fusidic acid (41%) and erythromycin (11%). The primary genetic mechanisms of fusidic acid resistance were carriage of fusC (57%) or mutations in fusA (38%). The most prevalent S. aureus lineage was ST1 (23%). All ST1 isolates carried fusC. Conclusions S. aureus fusidic acid resistance, caused by either fusA mutations or fusC gene carriage, is a major concern among AD patients. Resistant S. aureus might spread from the patients to the community, indicating the need to reduce the use of fusidic acid in the treatment of AD.

Temporal variation of Staphylococcus aureus clonal complexes in atopic dermatitis: a follow-up study

A strong link between disease severity and Staphylococcus aureus colonization of the skin has been reported in patients with atopic dermatitis (AD).