Journal Mobile

R Weller, WHI McLean
Journal Issue: 
Volume 38: Issue 1: 2008




Recent  genetic  findings  demonstrate  an  important  role  for  the epidermal protein filaggrin in the aetiology of atopic diseases, including asthma as well  as  eczema. Filaggrin  is  critical  to  the  conversion  of  keratinocytes  to  the protein/lipid  squames  that  compose  the stratum  corneum, the  outermost  barrier layer of the skin. In 2006, icthyosis vulgaris, a disease characterised by dry, scaly skin, was found to be a semi-dominant Mendelian condition due to mutations at two sites  (R501X  and  2282del4)  in  the  filaggrin  gene.  An  exceptionally  strong association  has  also  been  shown  between  these  two  mutations  and  the  most common distinct form of eczema, atopic dermatitis, in 12 independent European populations, with odds ratios varying between 2·8 and 13·4. No negative studies have been reported in Europe, although these two mutations are not associated with  AD  in  three  non-European  cohorts. Furthermore, FLG  null  mutations  have since been identified in European and non-European cohorts with AD. Asthma on a background of AD is related to FLG null status, but not in the absence of AD. A  primary  defect  in  skin  barrier  function  therefore  appears  to  underlie  atopic dermatitis  and  asthma. Immunological  changes  in  atopic  disease  are  probably secondary to enhanced antigen penetration through a deficient epidermal barrier.