The association between null mutations in the filaggrin gene and contact sensitization to nickel and other chemicals in the general population

Thyssen, Jacob P.; Johansen, Jeanne Duus; Linneberg, Allan; Menné, Torkil; Nielsen, Niels; Meldgaard, Michael; Szecsi, Pal B.; Stender, Steen; Carlsen, Berit Christina

doi:10.1111/j.1365-2133.2010.09708.x

Cited by 113 publications

(132 citation statements)

References 25 publications

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“…More recent studies have confirmed the association and identified additional mutations in the FLG gene that predispose to AD in European and Asian populations (64-67). FLG mutations have also been reported to be associated with atopic asthma, allergic rhinitis, nickel allergy, and food allergy (68)(69)(70)(71)(72)(73), suggesting that FLG mutation-associated SC barrier defects lead to increased numbers of episodes of percutaneous allergen exposure (Figure 2). Interestingly, FLG mutations are not associated with asthma without eczema (70,71), and most of the identified asthma-associated genes are not associated with AD (74,75), suggesting that atopic asthma is a distinguishable sub-entity.…”

Section: Major Players In Sc Barrier Dysfunctionmentioning

confidence: 99%

Epidermal barrier dysfunction and cutaneous sensitization in atopic diseases

Kubo¹,

Nagao²,

Amagai³

2012

J. Clin. Invest.

318

289

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Classic atopic dermatitis is complicated by asthma, allergic rhinitis, and food allergies, cumulatively referred to as atopic diseases. Recent discoveries of mutations in the filaggrin gene as predisposing factors for atopic diseases have refocused investigators' attention on epidermal barrier dysfunction as a causative mechanism. The skin's barrier function has three elements: the stratum corneum (air-liquid barrier), tight junctions (liquid-liquid barrier), and the Langerhans cell network (immunological barrier). Clarification of the molecular events underpinning epidermal barrier function and dysfunction should lead to a better understanding of the pathophysiological mechanisms of atopic diseases. IntroductionAtopic dermatitis (AD) is a chronic relapsing eczematous skin disorder that is frequently associated with elevated serum IgE levels and a family history of AD, allergic rhinitis, and/or asthma. Clinical manifestations of classic AD are dry skin and relapsing eczema, which usually start during early infancy or childhood and become complicated by food allergies, asthma, and/or allergic rhinitis during the first several years of life, in a process called "atopic march" (1). AD is highly prevalent in industrialized countries, where it affects approximately 15%-30% of children and 2%-10% of adults (2). The various observations of the disease indicate that AD has a complex etiology with genetic, immunological, and environmental aspects.Living organisms rely critically on surface barriers to isolate themselves from the external environment and to maintain homeostasis. While unicellular organisms are enclosed by cell membranes and cell walls, epithelial barrier structures, in several forms, cover the surfaces of multicellular organisms (3). In mammals, the airway and gastrointestinal tract are lined by simple epithelia covered with mucus. In contrast, the outer surface of the body is covered by a stratified epithelial cellular sheet called the epidermis, the outermost layer of which is cornified. Recent findings have shown that disruption of epithelial barrier systems are involved in the pathogenesis of immune disorders such as inflammatory bowel disease, asthma, and AD (4-12). In this review, we describe the barrier system of the epidermis, which is far more sophisticated than previously thought (13,14), and attempt to discuss its function with special focus on antigen penetration through these barriers and antigen capture by dendritic cells in the context of AD.

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Section: Major Players In Sc Barrier Dysfunctionmentioning

confidence: 99%

Epidermal barrier dysfunction and cutaneous sensitization in atopic diseases

Kubo¹,

Nagao²,

Amagai³

2012

J. Clin. Invest.

318

289

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“…Notably, individuals with a history of atopic dermatitis (AD) appear to be more susceptible to developing nickel allergy; this is not surprising, considering that filaggrin null mutations have been shown to be positively associated with nickel sensitization. 8,9 This fact advances the importance of contact allergy testing in children with recalcitrant or widespread severe AD, because such situations may indicate the presence of underlying or superimposed ACD. 10 Additionally, recognizing the risks of Ni-ACD associated with piercing may justify preemptive avoidance of nickel among patients with AD, to decrease sensitization and morbidity.…”

Section: Discussionmentioning

confidence: 97%

Belt Buckles—Increasing Awareness of Nickel Exposure in Children: A Case Report

et al. 2015

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Children, especially those with atopic dermatitis, are at risk for nickel sensitization and subsequent dermatitis from metal-containing objects, namely belt buckles. We describe allergic contact dermatitis in 12 children with peri-umbilical nickel dermatitis (with and without generalized involvement) caused by dimethylglyoxime-positive belt buckles. The patients' symptoms resolved with avoidance of the nickel-containing products.Nickel allergic contact dermatitis (Ni-ACD) has become increasingly recognized in the pediatric population, with prevalence rates in patch-tested populations of ∼25% throughout the last decade.

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“…Approximately 9% of people of European origin are carrying these variants [ 18,27 ] . More than 40 loss-of-function mutations within the fi laggrin gene have now been reported [ 30 ] .…”

Section: Filaggrin: the Multifunctional Proteinmentioning

confidence: 99%