異位性皮炎（濕疹），類固醇與症狀復發（Rebound）3

由於Michael J Cork教授的學說能夠對Rebound和Steroid Addiction現象作出合理解說，近年來有越來越多人接納這個學說的趨勢，而以下介紹的論文來自可以說是全世界最具權威性皮膚科刊物Journal of Investigative Dermatology。

Michael J Cork教授的有關Rebound現象和類固醇癮（Steroid Addiction）論文（下）

Michael J Cork教授在Epidermal Barrier Dysfunction in Atopic Dermatitis Michael J Cork etc. Journal of Investigative Dermatology 129, 1892–1908(June 2009)中除了警告不應隨意在輕度異位性皮炎個案使用類固醇，也不應長期使用類固醇，但同時也指出類固醇的短期使用對症狀有效，所以他的立場並非全面否定類固醇。他在文中寫道“The effect of topical corticosteroids on the epidermal barrier：Topical corticosteroids are successfully used to treat the immune hyperreactivity associated with AD; however, increasing evidence suggests that they do not address the epidermal barrier defect associated with this disorder. The skin of patients treated with TCS is up to 70% thinner compared with that of untreated controls. There is also a concomitant decrease in the amount of intercellular lipid lamellae and a reduced number of membrane-coated granules at the SC–SG interface. The effect of these changes on barrier function was shown by an elevation in TEWL from the skin of patients treated with TCS. The skin barrier defect has been observed for a range of treatment regimens using TCS, from the short-term use (3 days) of very potent TCS to the prolonged use (6 weeks) of very mild TCS. Rebound flare after discontinuation of TCS has similarities to that observed after other forms of barrier disruption, such as surfactants and tape stripping. Barrier disruption results in the initiation of cytokine cascade, followed by an inflammatory response. This suggests that a barrier defect triggers the inflammatory response after cessation of immune suppression by the use of TCS. Furthermore, steroids have been shown to induce the expression of the desquamatory protease, KLK7, which is associated with the barrier defect in AD. Taken together, although the use of TCS suppresses inflammation associated with AD, they concomitantly seem to further damage the skin barrier, thereby increasing the risk of developing further flares of the disease.” （外用皮質類固醇對表皮屏障的作用：外用皮質類固醇有效治療異位性皮炎［AD］帶來的過度免疫反應，但越來越多證據顯示類固醇對與該疾患相關的表皮屏障缺陷起不到作用。使用外用類固醇［TCS］治療過的患者皮膚與沒有使用過外用類固醇的皮膚對比之下，前者皮膚最多變薄70％。與此同時，還觀察到前者的細胞間脂質片層減少，位於角質－顆粒細胞介面的膜結合顆粒數目也減少。這些對表皮屏障機能產生的變化，均可從使用外用類固醇治療過的皮膚，透過經皮水分散失測試的結果觀察得到。目前已知從廣泛用到的TCS治療方案包括短期［3天］強效TCS治療以致長期［6星期］溫和TCS治療的結果都觀察到表皮屏障技能降低。停用TCS後出現的Rebound症狀與由界面活性劑和膠布剝離實驗導致的表皮屏障受損的情況相似。表皮屏障受損還引發細胞因子級聯反應，繼而產生發炎的現象，而這個現象就意味著停止使用TCS來抑制免疫的結果，受損表皮屏障會引發發炎反應。此外也有顯示，類固醇會促使與由AD引起的表皮屏障損傷有關連的脫皮蛋白酶和人激肽釋放酶7的生成。考慮到上述多種因素，可以說雖然TCS對AD而產生的發炎有抑制作用，但同時也會進一步破壞表皮屏障，因而增加原有疾患進一步惡化的風險。）