Sanja Kezic

Levels of filaggrin degradation products are influenced by both filaggrin genotype and atopic dermatitis severity

To cite this article: Kezic S, O’Regan GM, Yau N, Sandilands A, Chen H, Campbell LE, Kroboth K, Watson R, Rowland M, Irwin McLean WH, Irvine AD. Levels of filaggrin degradation products are influenced by both filaggrin genotype and atopic dermatitis severity. Allergy 2011; 66: 934–940.

Impact of atopic dermatitis and loss‐of‐function mutations in the filaggrin gene on the development of occupational irritant contact dermatitis

Background  Atopic dermatitis (AD) and loss‐of‐function mutations in the filaggrin gene (FLG) are both associated with chronic irritant contact dermatitis (ICD). As FLG mutations also are a major risk factor for AD, it is not clear whether FLG mutations are an independent risk factor for ICD or whether the risk is mediated by AD.

The effect of environmental humidity and temperature on skin barrier function and dermatitis.

Physicians are aware that climatic conditions negatively affect the skin. In particular, people living in equator far countries such as the Northern parts of Europe and North America are exposed to harsh weather during the winter and may experience dry and itchy skin, or deterioration of already existing dermatoses. We searched the literature for studies that evaluated the mechanisms behind this phenomenon. Commonly used meteorological terms such as absolute humidity, relative humidity and dew point are explained. Furthermore, we review the negative effect of low humidity, low temperatures and different seasons on the skin barrier and on the risk of dermatitis. We conclude that low humidity and low temperatures lead to a general decrease in skin barrier function and increased susceptible towards mechanical stress. Since pro‐inflammatory cytokines and cortisol are released by keratinocytes, and the number of dermal mast cells increases, the skin also becomes more reactive towards skin irritants and allergens. Collectively, published data show that cold and dry weather increase the prevalence and risk of flares in patients with atopic dermatitis.

Skin absorption through atopic dermatitis skin : a systematic review

Patients with atopic dermatitis (AD) have skin barrier impairment in both lesional and nonlesional skin. They are typically exposed daily to emollients and intermittently to topical anti‐inflammatory medicaments, thereby increasing the risk of developing contact allergy and systemic exposure to chemical ingredients found in these topical preparations. We systematically searched for studies that investigated skin absorption of various penetrants, including medicaments, in patients with AD, but also in animals with experimentally‐induced dermatitis. We identified 40 articles: 11 human studies examining model penetrants, 26 human studies examining AD drugs, and three animal studies. We conclude that patients with AD have almost twofold increased skin absorption compared with healthy controls. There is a need for well‐designed epidemiological and dermatopharmacokinetic studies that examine to what extent AD causes patients to be systemically exposed to chemicals compared with nonatopic dermatitis.

Changes in filaggrin degradation products and corneocyte surface texture by season

During the winter in northern countries, the risk of dermatitis is increased due to low temperature and humidity. Dermatitis is particularly common on weather‐exposed skin such as the cheeks and hands. Recently, increased numbers of unidentified nanosized protrusions on the corneocyte surface were associated with dermatitis and deficiency of natural moisturizing factor (NMF).

Effect of allergens and irritants on levels of natural moisturizing factor and corneocyte morphology

The irritant sodium lauryl sulfate (SLS) is known to cause a decrease in the stratum corneum level of natural moisturizing factor (NMF), which in itself is associated with changes in corneocyte surface topography.

Skin barrier and dry skin in the mature patient

Dry skin is the most common clinical manifestation of dermatologic diseases, and it presents with itching, redness, and desquamation-signs and clinical manifestations that are not only physically uncomfortable but also affect patients psychologically. The water content in the stratum corneum is largely dependent on the composition and amount of the intercellular lipids, which regulate the loss of water from the skin, and on the levels of hygroscopic substances of the natural moisturizing factors, which are responsible for retention of water in the stratum corneum. Prevention of water loss and penetration of potentially toxic substances and microorganisms into the body are the most important functions of the skin, which acts as a natural frontier between the inner organism and the environment. Skin barrier defects occur in several skin diseases, but the influence of aging on the skin barrier function is largely unknown and conflicting results have been reported. In this review, the structure and function of the barrier in relation to the aging process are discussed.

Atopic dermatitis patients with filaggrin loss-of-function mutations show good but lower responses to immunosuppressive treatment

Filaggrin (FLG) mutations are a strong risk factor to develop atopic dermatitis (AD). However, the relationship between FLG mutations and treatment outcome in AD has not been thoroughly studied. To investigate whether FLG mutations influence immunosuppressive treatment outcome in AD, we studied the effect of FLG mutations in patients with severe AD participating in a single blinded randomized controlled trial (RCT) with methotrexate (MTX) or azathioprine (AZA) during a 24 weeks treatment regimen.(1) Two years after randomization buccal mucosa swabs were collected from 36 of the 42 RCT patients (86%) to determine the FLG genotype status (R501X, 2282del4, R2447X, S3247X and 3321delA mutations). This article is protected by copyright. All rights reserved.

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.

The role of skin barrier in occupational contact dermatitis

Skin diseases represent one of the most common work‐related diseases and may have a detrimental effect on social, personal and occupational aspects of life. Contact dermatitis (CD), which comprises predominately irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD), accounts for vast majority of occupational skin diseases, especially in occupations associated with frequent skin contact with irritants and contact allergens. Although ICD and ACD have similar clinical manifestation, their pathophysiology and the role of the skin barrier are different. In ICD, perturbation of the skin barrier is the primary event which sets into motion diverse metabolic processes and triggers activation of innate immunity without the involvement of adaptive immune system. In ACD, a type IV hypersensitivity reaction induced by contact allergens, the skin barrier impairment may evoke innate signalling pathways during the sensitization phase required for the activation of T‐cell adaptive response. Thus, skin barrier impairment may increase the risk of ICD or ACD not only because of enhanced permeability and ingress of irritants and allergens but also by the generation of innate immune signal needed for the induction of allergic response. Hence, an efficient way to prevent CD is to avoid skin barrier damage in the workplace. This review focuses on the skin barrier, how it is affected by skin irritants and how its impairment contributes to the development of ICD and ACD.