Filaggrin mutations are strongly associated with contact sensitization in individuals with dermatitis

Thyssen, Jacob P.; Linneberg, Allan; Ross‐Hansen, Katrine; Carlsen, Berit Christina; Meldgaard, Michael; Szecsi, Pal B.; Stender, Steen; Menné, Torkil; Johansen, Jeanne Duus

doi:10.1111/cod.12021

Cited by 82 publications

(53 citation statements)

References 16 publications

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“…It was hypothesized that those subjects who have FLG mutations are more susceptible to the acquisition of CS to nickel following topical exposure. This was supported by a study showing strong nickel chelation by the histidine-rich filaggrin proteins [24]. CS to metals has been found to have a significant association with AD in both children and adults, probably due to the compromised chelating functions of AD skin.…”

Section: Factors That May Influence the Association Between Ad And Comentioning

confidence: 77%

Contact Allergy in Atopic Patients: What We Suspected and What We Know

Nardelli

Consigli

Berčík

et al. 2015

Curr Treat Options Allergy

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Section: Factors That May Influence the Association Between Ad And Comentioning

confidence: 77%

Contact Allergy in Atopic Patients: What We Suspected and What We Know

Nardelli

Consigli

Berčík

et al. 2015

Curr Treat Options Allergy

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“…The downregulation of fi laggrin expression by infl ammation may also be of great importance in other infl ammatory skin diseases such as contact dermatitis, in which infl ammation leads to a decreased skin barrier, and this in turn increases the infl ammatory reaction in a perpetual vicious circle, in which the risk of acquiring new allergies through the broken skin barrier is increased, as is the case in patients homozygous for the FLG mutations R501X and 2282del4 who have an odds Ration of 5.71 for sensitization to other allergens than nickel compared to healthy individuals [ 67 ].…”

Section: Discussionmentioning

confidence: 99%

Inflammatory-Driven Depletion of Filaggrin Proteins

Vestergaard

Deleuran

2014

Filaggrin

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Since the milestone publication by Palmer et al. in 2006 [ 1 ], in which it was shown that mutations in the fi laggrin gene ( FLG ), which codes for fi laggrin "fi lament aggregating protein," signifi cantly increase the risk of atopic dermatitis (AD), fi laggrin and barrier dysfunction have been the epicenter of AD research and other skin diseases with decreased skin barrier function. Filaggrin is important for the aggregation of keratin fi laments forming the impenetrable keratin layer in the stratum corneum of the epidermis and also for the hydration of the skin through the "natural moisturizing factors" (NMFs) [ 2 ]. The decreased barrier function caused by the lack of fi laggrin expression may increase the risk of allergic sensitization and thus offer a molecular background for the so-called atopic march, in which patients suffering from early childhood AD have a higher risk of developing asthma, rhinitis, and food allergies [ 3 ]. An interesting fact is that 44-85.8 % of AD patients do not carry an FLG mutation, but still all patients have a decreased skin barrier function [ 4 ], and that among patients carrying an FLG mutation, 40 % never show any signs of decreased skin barrier function [ 5 ].These results indicate that regulatory mechanisms other than null mutations in the FLG are responsible for the decreased skin barrier function in AD patients. Mutations in other genes involved in the skin barrier function have been linked to the development of AD such as SPINK5 (LEKTI), a serine protease inhibitor, which inhibits the

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“…Up to now, 3 studies have suggested a risk of developing contact allergy to nickel in subjects with FLG null mutations, indicating that a damaged skin barrier in persons with FLG null mutations can facilitate the penetration and presentation of nickel to antigen-presenting cells in the skin resulting in the development of easier and earlier sensitization [7,8,36]. Additionally, a recent study indicated that FLG mutation carriers with self-reported dermatitis have an increased risk of CS to substances other than nickel [37]. However, our previous study revealed a low frequency of common FLG null mutations in the Croatian population, suggesting that these mutations do not have a significant impact on the development and course of skin diseases, including ACD, in the Croatian and other populations with low penetrations of FLG mutations [38].…”

Section: Discussionmentioning

confidence: 99%

Occupational and Non-Occupational Allergic Contact Dermatitis: A Follow-Up Study

Macan

Rimac²,

Kežić

et al. 2013

Dermatology

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Background/Aims: The aim of this study was to obtain insight into the clinical course and prognosis of allergic contact dermatitis (ACD), including potential effects of genetic and environmental factors. Methods: Eighty-two patients with previously defined ACD acquired occupationally (OACD) or non-occupationally (NOACD) were patch retested and evaluated for the presence of persistent eczema, atopy and filaggrin mutations. Results: The crude risk for the persistence of a positive patch test (PT) reaction was 6.3 times higher (95% CI 3.63-11.0) for PT reactions assessed as ‘+++' compared to ‘++' reactions at the first PT. Among the categories of OACD, NOACD, age, gender, atopy, and the number of positive PT reactions at the first and second PT, only OACD (OR 10.0, 95% CI 1.95-51.2) and number of positive PT reactions at retesting (OR 3.85, 95% CI 1.57-9.44) were found to be predictors of persistent eczema. Conclusions: Occupationally acquired contact allergy was emphasized as the most important factor in predicting poor prognosis of ACD.

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Filaggrin mutations are strongly associated with contact sensitization in individuals with dermatitis

Abstract: FLG mutation carriers with self-reported dermatitis have an increased risk of contact sensitization to substances other than nickel, whereas FLG mutations alone may not, or may only slightly, increase the risk of sensitization.

Cited by 82 publications

References 16 publications

Contact Allergy in Atopic Patients: What We Suspected and What We Know

Contact Allergy in Atopic Patients: What We Suspected and What We Know

Inflammatory-Driven Depletion of Filaggrin Proteins

Occupational and Non-Occupational Allergic Contact Dermatitis: A Follow-Up Study

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