Classification of atopic hand eczema and the filaggrin mutations

Abstract

Hand eczema is a common disease with various risk factors of which atopic dermatitis is known to be one of the most important. Recently, two mutations in the gene coding for filaggrin, a protein important for the skin barrier, have repeatedly been shown to be associated with atopic dermatitis. Moreover, one study point towards an association between the filaggrin null alleles and the subgroup of patients having both hand eczema and atopic dermatitis. For the remainder of hand eczema patients, still unknown genetic risk factors exist. We propose that in future, classification of atopic hand eczema should distinguish between patients with and without the filaggrin null alleles and to further differentiate between associations with type I allergy, type IV allergy and exposure to irritants, respectively. Furthermore, we suggest future studies of atopic hand eczema to analyse for the filaggrin mutations. We believe this will increase the possibility of subgrouping this otherwise heterogenic disease and thereby enable a better phenotype-genotype characterization of hand eczema. This could improve the preventive initiatives, secure better information of patients about the prognosis for their disease, and possibly enable targeted treatment.

Filaggrin mutations may confer susceptibility to chronic hand eczema characterized by combined allergic and irritant contact dermatitis

“…The frequency of an atopic disease or family history, however, was slightly increased in our patients but did not reach statistical significance compared with patients without the mutations. Our data therefore also support the assumption that the genetic predisposition for hand eczema is largely independent of that for atopic eczema, although an increased susceptibility for CHE is conferred by atopy in general 22,33 …”

“…Our data therefore also support the assumption that the genetic predisposition for hand eczema is largely independent of that for atopic eczema, although an increased susceptibility for CHE is conferred by atopy in general. 22,33 In conclusion, our data support the idea that the heterozygous presence of either of the two FLG gene mutations, R501X or 2282del4, may contribute to a particular subtype of CHE which is characterized by a combination of irritant and allergic aspects. As proposed for atopic eczema a complete loss of filaggrin may increase the penetration of exogenous molecules such as bacterial toxins or allergens and thus promote eczema.…”

Reduced Inflammatory Threshold Indicates Skin Barrier Defect in Transglutaminase 3 Knockout Mice

“…Defects of structural proteins like filaggrin (Sandilands et al, 2007;Giwercman et al, 2008), or protease inhibitors (serine protease inhibitor Kazal-type 5) and cross-linking enzymes such as TG1, have been shown to be associated with damaged cornified cell envelope formation and an enhanced percutaneous sensitization rate (reviewed by Kubo et al, 2012). The role of TG3, a transglutaminase present in the cornified cell envelop and the uppermost layer of the stratum granulosum, however, remains largely unexplored in these processes.…”

Filaggrin Gene Defects and Dry Skin Barrier Function

“…Several studies have investigated whether certain fi laggrin variants might be associated with CHE in general. Some also investigated certain CHE subtypes [ 4,9,12,14,26 ] . Probably the most convincing evaluation of the possible association between hand eczema and fi laggrin null mutations was provided by a recent general population study including 3,471 adults.…”