Rafal E S, Griffiths C E, Ditre C M, Finkel L J, Hamilton T A, Ellis C N, Voorhees J J
Department of Dermatology, University of Michigan Medical Center, Ann Arbor 48109-0314.
N Engl J Med. 1992 Feb 6;326(6):368-74. doi: 10.1056/NEJM199202063260603.
The hyperpigmented lesions commonly called liver spots distress patients, in part because such lesions are associated with aging. We investigated their treatment with topical 0.1 percent tretinoin (retinoic acid).
Fifty-eight patients completed a 10-month randomized, double-blind study in which they applied either 0.1 percent tretinoin (n = 28) or vehicle (n = 30) cream daily to the face, upper extremities, or both. Fifteen patients who responded well were than randomly assigned to continue tretinoin therapy or use vehicle alone for six more months. Patients were evaluated by physical examination every month and by analysis of biopsy specimens of lesions obtained at base line and at the end of the 10-month trial.
After one month of treatment the patients treated with tretinoin had significant lightening of hyperpigmented lesions as compared with the patients who received vehicle (P less than 0.002). After 10 months, 20 (83 percent) of the 24 patients with facial lesions who were treated with tretinoin had lightening of these lesions, as compared with 8 (29 percent) of the 28 patients with facial lesions who received vehicle. The results for lesions of the upper extremities were similar. As compared with vehicle, tretinoin caused a significant decrease in the degree of epidermal pigmentation and increases in the degree of compaction of stratum corneum, thickness of the granular cell layer, and epidermal thickness. Reductions in epidermal pigmentation evident on histologic analysis were significantly correlated with the degree of clinical lightening of lesions (r = -0.53, P less than 0.0001). During the 6-month follow-up study, specifically identified lesions that had disappeared during the first 10 months of tretinoin treatment did not return in any patient, and six of seven patients who continued to use tretinoin had further improvement.
Topical 0.1 percent tretinoin significantly improves both clinical and microscopical manifestations of liver spots; these lesions do not return for at least six months after therapy is discontinued.
色素沉着过度性损害俗称老年斑，常令患者苦恼，部分原因是此类损害与衰老相关。我们研究了外用0.1%维甲酸（视黄酸）对此类损害的治疗效果。
58例患者完成了一项为期10个月的随机双盲研究，他们每日将0.1%维甲酸乳膏（n = 28）或赋形剂乳膏（n = 30）涂于面部、上肢或两者。15例反应良好的患者随后被随机分配继续使用维甲酸治疗或单独使用赋形剂再治疗6个月。每月对患者进行体格检查，并对基线时及10个月试验结束时获取的损害活检标本进行分析。
治疗1个月后，与接受赋形剂治疗的患者相比，使用维甲酸治疗的患者色素沉着过度性损害明显减轻（P < 0.002）。10个月后，接受维甲酸治疗的24例面部损害患者中有20例（83%）损害减轻，而接受赋形剂治疗的28例面部损害患者中有8例（29%）损害减轻。上肢损害的结果相似。与赋形剂相比，维甲酸可使表皮色素沉着程度显著降低，角质层致密程度、颗粒细胞层厚度和表皮厚度增加。组织学分析显示的表皮色素沉着减少与损害的临床减轻程度显著相关（r = -0.53，P < 0.0001）。在6个月的随访研究中，在维甲酸治疗的前10个月消失的特定损害在任何患者中均未复发，继续使用维甲酸的7例患者中有6例有进一步改善。
外用0.1%维甲酸可显著改善老年斑的临床和显微镜下表现；停止治疗后至少6个月这些损害不会复发。
