Fleckman Philip, Brumbaugh Steven
Division of Dermatology, Department of Medicine, University of Washington, Seattle, WA 98195-6524, USA.
Exp Dermatol. 2002 Aug;11(4):327-36. doi: 10.1034/j.1600-0625.2002.110406.x.
The clinical diagnosis of ichthyosis vulgaris (IV) can be difficult. Abnormalities in the granular layer and the ultrastructure of keratohyalin granules (KHG) suggest that morphology may be helpful. To clarify morphologic findings in IV, 41 clinically affected individuals and 21 unaffected family members or age- and sex-matched controls were studied by light microscopy. In these, the granular layer was totally absent in approximately 50% of affected individuals, while present in all controls. Forty-seven individuals in the light microscopy group were also studied by electron microscopy. Keratohyalin granules were absent in all affected individuals lacking the granular layer by light microscopy. Clinical severity usually correlated with the lack of a granular layer and KHG. Absence of the granular layer was consistent in different anatomic sites and in serial biopsies taken over a 1-3-year period. In a subset of clinically affected, unrelated subjects with moderate to severe involvement, four out of 11 (36%) had similar findings. Keratinocytes cultured from affected individuals with no KHG expressed virtually no detectable profilaggrin protein in vitro. The data suggest that a subset of individuals with moderate to severe IV have a consistently absent granular layer and KHG. Absence of the granular layer and lack of KHG correlated almost perfectly; thus light microscopy offers a convenient means of identifying this subtype of IV. However, both morphologic types of IV were observed within single families. Therefore, the relationship between granular layer abnormalities and IV is complex and requires the study of more affected families. One interpretation of the data is that IV is a multigenic disorder in which one of the genes alters profilaggrin expression. We propose this clinical and histologic phenotype as useful for identifying the gene(s) involved and also for determining whether it represents a modifier or a major locus of the disorder.
寻常型鱼鳞病（IV）的临床诊断可能具有挑战性。颗粒层及透明角质颗粒（KHG）超微结构的异常表明，形态学特征可能有助于诊断。为了阐明IV的形态学表现，我们通过光学显微镜对41名临床确诊患者以及21名未患病的家庭成员或年龄、性别匹配的对照者进行了研究。结果发现，约50%的患者颗粒层完全缺失，而所有对照者均存在颗粒层。光学显微镜组中的47名个体还接受了电子显微镜检查。光学显微镜下颗粒层缺失的所有患者，电子显微镜检查均未发现透明角质颗粒。临床严重程度通常与颗粒层及透明角质颗粒的缺失相关。颗粒层缺失在不同解剖部位以及1 - 3年期间的连续活检中均保持一致。在一部分临床确诊、无亲缘关系且中重度受累的患者中，11人中有4人（36%）有类似表现。从无透明角质颗粒的患者中培养的角质形成细胞在体外几乎检测不到前丝聚合蛋白。数据表明，一部分中重度IV患者始终存在颗粒层及透明角质颗粒缺失。颗粒层缺失与透明角质颗粒缺乏几乎完全相关；因此，光学显微镜提供了一种识别该IV亚型的便捷方法。然而，在单个家族中观察到了两种形态学类型的IV。因此，颗粒层异常与IV之间的关系较为复杂，需要对更多受累家族进行研究。对这些数据的一种解释是，IV是一种多基因疾病，其中一个基因改变了前丝聚合蛋白的表达。我们认为这种临床和组织学表型有助于识别相关基因，也有助于确定它是该疾病的修饰基因还是主要基因座。
