PDF(Pubmed)
Abstract：
Several patients with cutaneous adverse drug reactions exhibit extracutaneous organ damages, and it becomes severe in a few patients resulting in death due to multiorgan failure. Understanding the sequential changes in various organs in patients with cutaneous eruption following drug administration will help understand disease onset and progression, aiding the development of prevention strategies and interventions. Therefore, we aimed to understand the effects of abacavir (ABC) on various organs in patients with ABC-induced eruptions by evaluating its effects in a mouse model. We found pathological changes in various organs of HLA-B*57:01 transgenic mice (B*57:01-Tg) following oral administration of ABC (20 mg/body/day). B*57:01-Tg exhibited a significant body weight decrease from day 1 of ABC administration, and reddening of the auricle was observed from day 5, and approximately 2/3 mice died by day 7. Histopathological examination revealed severe thymic atrophy after day 3, infiltration of inflammatory cells, predominantly lymphocytes with neutrophils, not only in the skin but also in the liver, kidney, and lung after day 5, and an increased number of lymphocytes with enlarged nuclei and granulocytic hematopoiesis were observed in the spleen after day 5. Blood chemistry revealed that albumin/globulin ratio was below 1.0 on day 5, reflecting a systemic inflammatory response, and the aspartate aminotransferase concentration rose to 193 ± 93.0 U/L on day 7, suggesting that cell damage may have occurred in various organs including liver accompanying inflammatory cell infiltration. These examinations of a mouse model of ABC-induced skin eruption show that disorders in various organs other than the skin should be considered and provide insights into the unexpected early systemic responses dependent on HLA-B*57:01.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s43188-023-00220-1.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s43188-023-00220-1.
摘要：
一些皮肤药物不良反应的患者表现为皮肤外器官损害，并且在少数患者中变得严重，导致由于多器官衰竭而死亡。了解药物治疗后皮肤疹患者各种器官的顺序变化将有助于了解疾病的发作和进展，协助制定预防战略和干预措施。因此,我们旨在通过在小鼠模型中评估阿巴卡韦（ABC）对ABC引起的皮疹患者的各种器官的影响。我们发现口服ABC（20mg/体/天）后，HLA-B*57：01转基因小鼠（B*57：01-Tg）的各个器官发生病理变化。B*57：01-Tg从ABC给药的第1天开始表现出明显的体重下降，从第5天开始观察到耳廓变红，到第7天大约有2/3的小鼠死亡。组织病理学检查显示第3天后胸腺严重萎缩，炎症细胞浸润，主要是带有中性粒细胞的淋巴细胞，不仅在皮肤中，而且在肝脏中，肾,和第5天后的肺，第5天后在脾脏中观察到淋巴细胞数量增加，细胞核增大和粒细胞造血。血液化学显示，白蛋白/球蛋白比值在第5天低于1.0，反映了全身炎症反应，天冬氨酸转氨酶浓度在第7天升至193±93.0U/L，表明细胞损伤可能发生在包括肝脏在内的各种器官中，伴随着炎症细胞浸润。对ABC诱导的皮肤爆发的小鼠模型的这些检查表明，应考虑除皮肤以外的各种器官中的疾病，并提供对依赖于HLA-B*57:01的意外早期全身反应的见解。
■在线版本包含补充材料，可在10.1007/s43188-023-00220-1获得。
■在线版本包含补充材料，可在10.1007/s43188-023-00220-1获得。
