Genotype, Clinical Course, and Therapeutic Decision Making in 76 Infants with Severe Generalized Junctional Epidermolysis Bullosa
Genotype, Clinical Course, and Therapeutic Decision Making in 76 Infants with Severe Generalized Junctional Epidermolysis Bullosa
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DOI：
10.1016/j.jid.2016.06.609
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发表时间：
2016-11-01
影响因子：
6.5
通讯作者：
Schneider, Holm
中科院分区：
文献类型：
--
作者：
Hammersen, Johanna;Has, Cristina;Schneider, Holm
严重的泛发性交界性大疱性表皮病是一种致命的遗传性水疱病，通常采用姑息治疗。异基因干细胞移植（SCT）已被提出作为一种治疗方法，但没有临床证据。对2000-2015年出生的76例重度全身性交界性大疱性表皮松解症患者的决策进行了回顾性评价。诊断是基于皮肤活检中缺乏层粘连蛋白-332。发生率为1/150，000，重度全身性交界性大疱性表皮松解症的发生率高于先前发表的文献。在层粘连蛋白-332基因中检测到11个尚未报道的突变。尽管LAMB 3突变c. 1903 C>T比其他人活得更长，预期寿命大大缩短（10.8个月对4.6个月）。大多数病人都没有康复。在两名最初体重增加正常的患者中，决定采用单倍体骨髓或外周血进行螺旋CT。尽管皮肤糜烂短暂增加，但两名受试者的临床状态在SCT后稳定了数周，但最终恶化。移植细胞，但没有层粘连蛋白-332，检测皮肤活检。患者分别在SCT后96天和129天死亡，其中一名患者在接受额外的皮肤移植后死亡。SCT治疗严重的全身性交界性大疱性表皮松解症是最后的尝试，仍缺乏有效性的证据。
Severe generalized junctional epidermolysis bullosa, a lethal hereditary blistering disorder, is usually treated by palliative care. Allogeneic stem cell transplantation (SCT) has been proposed as a therapeutic approach, yet without clinical evidence. Decision making was evaluated retrospectively in 76 patients with severe generalized junctional epidermolysis bullosa born in the years 2000-2015. The diagnosis was based on the absence of laminin-332 in skin biopsies. With an incidence of 1 of 150,000, severe generalized junctional epidermolysis bullosa occurred more often than published previously. Eleven as yet unreported mutations in the laminin-332 genes were detected. Although patients homozygous for the LAMB3 mutation c. 1903C>T lived longer than the others, life expectancy was greatly diminished (10.8 vs. 4.6 months). Most patients failed to thrive. In two patients with initially normal weight gain, the decision for SCT from haploidentical bone marrow or peripheral blood was made. Despite transiently increasing skin erosions, the clinical status of both subjects stabilized for several weeks after SCT, but finally deteriorated. Graft cells, but no laminin-332, were detected in skin biopsies. The patients died 96 and 129 days after SCT, respectively, one of them after receiving additional skin grafts. Treatment of severe generalized junctional epidermolysis bullosa by SCT is a last-ditch attempt still lacking proof of efficacy.