Arita Ken, Akiyama Masashi, Tsuji Yukiko, Onozuka Takashi, Shimizu Hiroshi
Department of Dermatology, Hokkaido University Graduate School of Medicine, North 15 West 7, Kita-ku, Sapporo 060-8638, Japan.
Acta Derm Venereol. 2003;83(4):266-70. doi: 10.1080/00015550310016517.
Erythrokeratoderma variabilis, characterized by migrating erythema and fixed keratotic plaques, is a rare congenital disorder which has recently been connected with connexin (Cx)30.3 or Cx31 gene mutations. We present a 9-month-old Japanese girl who exhibited the typical clinical features of the disease, but carried no Cx30.3 or Cx31 gene mutations. Histopathologically, regular acanthosis with hyperkeratosis and hypergranulosis was observed in her lesional skin. Upregulation of involucrin and loricrin expression, and a weak expression of Cx26 was immunohistochemically observed in the upper spinous and granular layers. Electron microscopy revealed no abnormality in the keratin filaments, cornified cell envelope or gap junctions. Direct sequencing revealed no pathogenetic mutations in the Cx26, Cx30.3, Cx31 or Cx31.1 genes in this patient. The results indicate that erythrokeratoderma variabilis is pathologically heterogeneous, and that abnormalities in keratinization other than Cx30.3 and 31 gene mutations may underlie some forms of this disease.
可变性红斑角化病以游走性红斑和固定性角化斑块为特征，是一种罕见的先天性疾病，最近已与连接蛋白（Cx）30.3或Cx31基因突变相关。我们报告一名9个月大的日本女孩，她表现出该病的典型临床特征，但未携带Cx30.3或Cx31基因突变。组织病理学检查显示，其皮损处有规则的棘层肥厚伴角化过度和颗粒层增厚。免疫组织化学观察到，在棘层上部和颗粒层中，兜甲蛋白和loricrin表达上调，Cx26表达较弱。电子显微镜检查显示，角蛋白丝、角化包膜或缝隙连接无异常。直接测序显示，该患者的Cx26、Cx30.3、Cx31或Cx31.1基因无致病突变。结果表明，可变性红斑角化病在病理上具有异质性，除Cx30.3和31基因突变外，其他角化异常可能是该病某些类型的发病基础。
