Department of Dermatology, National Center for Global Health and Medicine, Tokyo, Japan.
Department of Regenerative Medicine, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
J Dermatol. 2020 May;47(5):554-558. doi: 10.1111/1346-8138.15296. Epub 2020 Mar 10.
Mal de Meleda (MDM) is a rare, autosomal recessive form of palmoplantar keratoderma due to mutations in the gene, encoding for secreted lymphocyte antigen 6/urokinase-type plasminogen activator receptor related protein 1 (SLURP1). We report a four-year-old Taiwanese MDM female case whose biopsy specimen of hyperkeratotic lesions showed abnormal keratinization and cutaneous inflammation with characteristic transmission electron microscopic (TEM) findings and immunostaining results. The patient presented with pruritic and severely hyperkeratotic plaques on the bilateral palms and soles whichwere fringed with erythematous scaly areas. A homozygous c.256 G>A mutation, predicting a conversion of p.Gly86Arg, in SLURP1gene was detected. Histopathological examinations showed marked hyperkeratosis, acanthosis and hypergranulosis in the epidermis, accompanied by perivascular lymphocytic infiltrates in the dermis. The whole layers of the epidermis and perivascular infiltrates of the dermis were stained positive with anti-tumor necrosis factor alpha (TNFα) antibody in the biopsy specimen from the sole and the ankle. TEM examination of the biopsy specimen from the plantar hyperkeratotic plaque showed various-sized vacuoles surrounding nuclei of many keratinocytes in the spinous layer. In addition, there were numerous irregular keratohyaline granules in the granular layer. Several microorganisms and many lipid-like droplets were found in the thickened cornified layer. SLURP1 protein is known as a marker of late differentiation, predominantly expressed in the granular layer, and also known to have an inhibitory effect on TNFα release. Our results exhibited excessive TNFα expression in keratinocytes and perivascular infiltrates of the dermis, and several characteristic morphological observations of keratinocytes in MDM.
遗传性汗孔角化症（MDM）是一种罕见的常染色体隐性掌跖角化病，由编码分泌型淋巴细胞抗原 6/尿激酶型纤溶酶原激活物受体相关蛋白 1（SLURP1）的基因突变引起。我们报告了一例四周岁的台湾 MDM 女性病例，其角化过度病变的活检标本显示异常角化和皮肤炎症，具有特征性的透射电镜（TEM）发现和免疫染色结果。患者双侧手掌和足底出现瘙痒和严重角化过度斑块，边缘为红斑鳞屑区。在 SLURP1 基因中检测到纯合 c.256 G>A 突变，预测 p.Gly86Arg 转换。组织病理学检查显示表皮明显角化过度、棘层肥厚和过度颗粒化，真皮伴有血管周围淋巴细胞浸润。足底角化过度斑块活检标本的表皮全层和真皮血管周围浸润均用抗肿瘤坏死因子-α（TNFα）抗体染色阳性。足底角化过度斑块活检标本的 TEM 检查显示棘层许多角质形成细胞核周围有各种大小的空泡，颗粒层有大量不规则的角蛋白颗粒。增厚的角化层中发现了几个微生物和许多类脂样小滴。SLURP1 蛋白是晚期分化的标志物，主要在颗粒层表达，也被认为具有抑制 TNFα 释放的作用。我们的结果显示角质形成细胞和真皮血管周围浸润中 TNFα 表达过度，以及 MDM 中角质形成细胞的几个特征形态学观察。
