Division of Clinical Dermatology and Cutaneous Science, Department of Medicine, Dalhousie University, Halifax, Canada.
Division of Dermatology and Experimental Medicine, Department of Medicine, McGill University, Montreal, Canada.
Contact Dermatitis. 2019 Jun;80(6):354-358. doi: 10.1111/cod.13268. Epub 2019 Apr 10.
Polysensitivity is defined as three or more positive patch test reactions. The role of filaggrin gene (FLG) loss-of-function mutations in patients with polysensitivity has not been studied when barrier bypass and possible preceding barrier damage have been excluded.
To determine whether FLG loss of function mutations play a role in patients with multiple contact sensitivities when barrier bypass is excluded.
One hundred and sixty-nine patients with three or more, non-cross-reacting, positive patch test reactions were prospectively enrolled in this study. Exclusion criteria were a history of hand dermatitis, nickel and metal implants, and stasis dermatitis. Subjects were patch tested with the North American extended patch test series, and with other relevant haptens. DNA was obtained and sequenced for the following FLG loss-of-function mutations: R501X, 2282del4, R2447X, and S3247X.
One hundred and sixty-five patients were genotyped for the four FLG mutations. There was a significant association between R501X mutation and polysensitivity. For the other three tested mutations, there were no significant associations with polysensitivity. When all mutations were combined, there was a significant association between loss-of-function FLG mutations and polysensitivity in patients with a history of atopic dermatitis.
When skin barrier bypass is excluded, there is a significant association between polysensitivity and FLG loss-of-function mutations.
多敏是指三种或以上的阳性斑贴试验反应。当排除了旁路和潜在的屏障损伤后，丝聚蛋白基因（FLG）无功能突变在多敏患者中的作用尚未得到研究。
当排除旁路时，确定 FLG 功能丧失突变是否在多种接触敏感患者中起作用。
本前瞻性研究纳入了 169 例三种或以上非交叉反应阳性斑贴试验反应的患者。排除标准为手部湿疹病史、镍和金属植入物以及淤滞性皮炎。受试者接受了北美扩展斑贴试验系列和其他相关变应原的斑贴试验。获取并对以下 FLG 功能丧失突变进行 DNA 测序：R501X、2282del4、R2447X 和 S3247X。
对 165 例患者的四种 FLG 突变进行了基因分型。R501X 突变与多敏显著相关。对于另外三种测试的突变，与多敏无显著相关性。当所有突变合并时，在有特应性皮炎病史的患者中，无功能 FLG 突变与多敏之间存在显著相关性。
当排除皮肤屏障旁路时，多敏与 FLG 功能丧失突变之间存在显著相关性。
