Kyllönen H, Remitz A, Mandelin J M, Elg P, Reitamo S
Department of Dermatology, Hospital for Skin and Allergic Diseases, University of Helsinki, 00250, Finland.
Br J Dermatol. 2004 Jun;150(6):1174-81. doi: 10.1111/j.1365-2133.2004.06017.x.
Topical corticosteroids decrease collagen synthesis during short-term treatment and can induce skin atrophy when applied over the long term. In contrast, short-term tacrolimus ointment therapy does not affect collagen synthesis.
Our aim was to evaluate the long-term effects of 0.1% tacrolimus ointment on collagen synthesis and on skin thickness in adults with moderate to severe atopic dermatitis (AD) and to compare the findings with the effects of conventional steroid-based therapy.
Fifty-six patients with AD were treated with 0.1% tacrolimus ointment in a 1-year, open-label, prospective clinical trial. Thirty-six patients with AD applied conventional steroid-based therapy and 27 healthy subjects were recruited as controls. The primary endpoint was the change in levels of procollagen propeptides I and III measured by radioimmunoassay between baseline and month 12. Additional endpoints included the change in skin thickness measured by ultrasound between baseline and month 12.
Procollagen propeptide baseline values were significantly lower in the group to be treated with tacrolimus ointment than in healthy controls. One-year treatment with tacrolimus ointment was associated with an increase in collagen synthesis; the median increase in combined procollagen propeptide levels was 272 micro g L-1 (+ 140.9%, P < 0.001) and was accompanied by a significant increase in skin thickness. In three patients with visible skin atrophy, this condition ameliorated. Corticosteroid-based therapy had no significant effect on collagen synthesis; the median increase in combined procollagen propeptide levels was 11 micro g L-1 (+ 3.9%). A significant reduction in skin thickness was demonstrated.
Long-term tacrolimus ointment therapy in patients with AD is nonatrophogenic and reverses corticosteroid-induced skin atrophy.
局部用皮质类固醇在短期治疗期间会减少胶原蛋白合成，长期使用可导致皮肤萎缩。相比之下，短期使用他克莫司软膏疗法不影响胶原蛋白合成。
我们的目的是评估0.1%他克莫司软膏对中度至重度特应性皮炎（AD）成人患者胶原蛋白合成和皮肤厚度的长期影响，并将结果与传统类固醇疗法的效果进行比较。
56例AD患者在一项为期1年的开放标签前瞻性临床试验中接受0.1%他克莫司软膏治疗。36例AD患者采用传统类固醇疗法，招募27名健康受试者作为对照。主要终点是通过放射免疫测定法测量的基线至第12个月期间前胶原肽I和III水平的变化。其他终点包括通过超声测量的基线至第12个月期间皮肤厚度的变化。
他克莫司软膏治疗组的前胶原肽基线值显著低于健康对照组。他克莫司软膏治疗1年与胶原蛋白合成增加相关；前胶原肽联合水平的中位数增加为272μg/L（+140.9%，P<0.001），并伴有皮肤厚度显著增加。3例有可见皮肤萎缩的患者，这种情况有所改善。基于皮质类固醇的疗法对胶原蛋白合成无显著影响；前胶原肽联合水平的中位数增加为11μg/L（+3.9%）。皮肤厚度有显著降低。
AD患者长期使用他克莫司软膏疗法不会引起皮肤萎缩，且可逆转皮质类固醇引起的皮肤萎缩。
