TREATMENT OF SKIN BARRIER DYSFUNCTION
Therapies for barrier dysfunction are still limited. Semi-occlusive emollients, especially petrolatum, reduce transepidermal water loss, although less effectively than native stratum corneum lipids. Impermeable and vaporpermeable dressings can provide nearly complete occlusion and are as effective as potent topical corticosteroids in the treatment of psoriasis, but are normally limited to small treatment areas. Moreover, these treatments are no substitute for the stratum corneum as a microbial barrier – they are applied on top of (superficial to) the microbiome, thereby providing an underlying moist environment that facilitates microbial growth and enhanced penetration. This explains why emollients and occlusive dressings increase the risk of skin infections. Of note, topical probiotics can have beneficial effects on skin barrier homeostasis.
Targeted therapy of barrier dysfunction must address the underlying cause. While inflammation can be treated with anti-inflammatory and immunomodulatory drugs, a new class of therapeutic agents that addresses defects in lipid metabolism is emerging. For example, porokeratosis and CHILD syndrome, both resulting from defects in cholesterol synthesis, have been reported to improve following application of cholesterol plus lovastatin (the latter blocks accumulation of pathogenic lipid precursors). Ceramide-based, triple-lipid mixtures are employed to address defective barrier function. Increasing knowledge about the pathophysiology of skin barrier-driven diseases should offer major opportunities for novel therapies.
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Drug Delivery