Mouton R W, Jordaan H F, Schneider J W
Department of Dermatology, Faculty of Health Sciences, University of Stellenbosch and Tygerberg Hospital, PO Box 19063, Tygerberg 7505, South Africa.
Clin Exp Dermatol. 2004 Jan;29(1):8-14. doi: 10.1111/j.1365-2230.2004.01421.x.
Pigmentary disorders are recognized adverse effects of the semi-synthetic tetracycline derivative antibiotic, minocycline. Three distinct types of minocycline-induced cutaneous pigmentation have been described. Type I, blue-black pigmentation confined to sites of scarring or inflammation on the face; Type II, blue-grey circumscribed pigmentation of normal skin of the lower legs and forearms; and Type III, diffuse muddy brown pigmentation of normal skin accentuated in sun-exposed areas. We report two patients with acne vulgaris with a fourth type of minocycline-induced cutaneous pigmentation. They presented with circumscribed blue-grey pigmentation within acne scars confined to the back. Histology showed pigment within dendritic cells, and extracellularly throughout the dermis. Histochemistry identified a calcium containing melanin-like substance. Iron was absent. Immunohistochemistry confirmed some pigment-containing cells to be macrophages. Electron microscopy demonstrated electron-dense granules, free and membrane-bound, within macrophages and fibroblast-like cells. Energy-dispersive X-ray analysis confirmed the presence of calcium. Iron was absent. This fourth type of cutaneous minocycline hyperpigmentation may be a variant of Type I, but based on clinical, pathological and microanalytical differences, appears to be a new entity. The pigment may be a drug metabolite-protein complex chelated with calcium, or an insoluble minocycline-melanin complex. We propose a classification of cutaneous minocycline pigmentation based on clinico-pathological criteria.
色素沉着紊乱是半合成四环素衍生物抗生素米诺环素公认的不良反应。已描述了三种不同类型的米诺环素诱导的皮肤色素沉着。I型，蓝黑色色素沉着局限于面部瘢痕或炎症部位；II型，小腿和前臂正常皮肤的蓝灰色局限性色素沉着；III型，正常皮肤的弥漫性泥褐色色素沉着，在阳光暴露部位加重。我们报告了两名寻常痤疮患者出现了第四种米诺环素诱导的皮肤色素沉着。他们的背部痤疮瘢痕内出现局限性蓝灰色色素沉着。组织学显示色素存在于树突状细胞内，并在整个真皮的细胞外。组织化学鉴定出一种含钙的类黑色素物质。不含铁。免疫组织化学证实一些含色素细胞为巨噬细胞。电子显微镜显示巨噬细胞和成纤维细胞样细胞内有游离和膜结合的电子致密颗粒。能量色散X射线分析证实存在钙。不含铁。这种第四种类型的皮肤米诺环素色素沉着可能是I型的一种变体，但基于临床、病理和微观分析差异，似乎是一种新的实体。色素可能是与钙螯合的药物代谢物-蛋白质复合物，或不溶性米诺环素-黑色素复合物。我们基于临床病理标准提出了一种皮肤米诺环素色素沉着的分类方法。
