New perspectives on epidermal barrier dysfunction in atopic dermatitis: gene-environment interactions.
Atopic dermatitis (AD) is a multifactorial, chronic inflammatory skin disorder in which genetic mutations and cutaneous hyperreactivity to environmental stimuli play a causative role. Genetic mutations alone might not be enough to cause clinical manifestations of AD, and this review will propose a new perspective on the importance of epidermal barrier dysfunction in genetically predisposed individuals, predisposing them to the harmful effects of environmental agents. The skin barrier is known to be damaged in patients with AD, both in acute eczematous lesions and also in clinically unaffected skin. Skin barrier function can be impaired first by a genetic predisposition to produce increased levels of stratum corneum chymotryptic enzyme. This protease enzyme causes premature breakdown of corneodesmosomes, leading to impairment of the epidermal barrier. The addition of environmental interactions, such as washing with soap and detergents, or long-term application of topical corticosteroids can further increase production of stratum corneum chymotryptic enzyme and impair epidermal barrier function. The epidermal barrier can also be damaged by exogenous proteases from house dust mites and Staphylococcus aureus. One or more of these factors in combination might lead to a defective barrier, thereby increasing the risk of allergen penetration and succeeding inflammatory reaction, thus contributing to exacerbations of this disease.
Cork
Michael J
MJ
Pediatric Dermatology Clinic, Children's Hospital, Sheffield S10 2RX, UK. m.j.cork@sheffield.ac.uk
Robinson
Darren A
DA
Vasilopoulos
Yiannis
Y
Ferguson
Adam
A
Moustafa
Manar
M
MacGowan
Alice
A
Duff
Gordon W
GW
Ward
Simon J
SJ
Tazi-Ahnini
Rachid
R
D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology; D003876:Dermatitis, Atopic / Q000378:metabolism*; D003902:Detergents / Q000494:pharmacology; D004777:Environment; D004817:Epidermis / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007610:Kallikreins / Q000235:genetics / Q000502:physiology; D010447:Peptide Hydrolases / Q000494:pharmacology; D053491:Proteinase Inhibitory Proteins, Secretory; D000074163:Serine Peptidase Inhibitor Kazal-Type 5; D013211:Staphylococcus aureus / Q000201:enzymology
D000305:Adrenal Cortex Hormones; D002352:Carrier Proteins; D003902:Detergents; D053491:Proteinase Inhibitory Proteins, Secretory; C120650:SPINK5 protein, human; D000074163:Serine Peptidase Inhibitor Kazal-Type 5; D010447:Peptide Hydrolases; C082472:KLK7 protein, human; D007610:Kallikreins