The Effect of High Dose Systemic Steroid and its Long-term Usage on the Skin Barrier of Hairless Mice

Lee, Jin Wook; Bak, Hana; Ahn, Sung Ku; Choi, Eung Ho; Lee, Seung Hun

Abstract

BACKGROUND
Prolonged exposure of topical and systemic corticosteroid to skin can result in well-recognized cutaneous abnormalities including cutaneous atrophy, easy bruisibility, increased skin fragility, and increased risk of infection. Skin barrier impairment is also reported as a steroid-induced side effect. A major function of the skin is the formation of a permeability barrier between the external milieu and the organism. Recent studies have shown that chronic corticosteroid negatively impacts epidermal barrier function. As well as this topical corticosteroid not only has antiproliferative actions but also inhibits the differentiation of the epidermis, resulting in structural defects in the epidermis. OBJECT: We wanted to determine whether high dose systemic steroid injection would display adverse effects, specifically on; epidermal functions, permeability barrier homeostasis and stratum corneum integrity and cohesion. The basis for such changes was also to be determined. MATERIAL AND METHODS: Systemic steroid was administered by injecting each hairless mouse, 8-10 week of age, intraperitoneally with 0.3 mg triamcinolone acetonide, two times per week for five weeks. For the controlled hairless mice, 0.9% normal saline was administered by the same method of injection. Every week, transepidermal water loss (TEWL) was checked and skin biopsies were taken. Skin specimens were prepared for electron microscopy using both 0.25% ruthenium tetroxide and 4% osmium tetroxide postfixation. For light microscopy staining hematoxylin-eosin and ion capture cytochemistry was used. RESULTS: The results were as follows; 1. From about 1 week onwards, high dose systemic steroid usage produced visible cutaneous changes and significantly increased the TEWL in the group of 0.3 mg triamcinolone acetate injected hairless mice compared with the control. 2. Light microscopic observations of the steroid-injected hairless mice showed gradual thinning of the epidermis from about 2 weeks onwards, compared with the control. Loss of stratum corneum was also observed in the steroid injected hairless mice. 3. The ruthenium tetroxide staining of high dose systemic steroid treated specimens revealed that the lipid bilayer was impaired and fragmented from about 3 weeks. Intercellular spaces were widened and the lipid bilayer either disappeared or showed damage when compared with the control. 4. From about 3weeks onwards. electron microscopic studies revealed, not only a marked decrease in the number of lamellar bodies, but also an abnormal transformation of lamellar bodies in the steroid injected hairless mice compared with the control. 5. Throughout the five weeks, the calcium gradient gradually disappeared in the 0.3mg triamcinolone injected hairless mice compared with the control. Consequently, high dose systemic steroid use results in barrier dysfunction and morphological abnormalities.