Maeda-Aoyama Natsuki, Hamada-Ode Kazu, Taniguchi Yoshinori, Nishikawa Hirofumi, Arii Kaoru, Nakajima Kimiko, Fujimoto Shimpei, Terada Yoshio
Department of Endocrinology, Metabolism, Nephrology and Rheumatology, Kochi Medical School Hospital, Nankoku.
Department of Internal Medicine, Kochi Red Cross Hospital, Kochi.
Medicine (Baltimore). 2020 Feb;99(6):e19051. doi: 10.1097/MD.0000000000019051.
Adult-onset Still disease (AOSD), a systemic inflammatory disorder, is characterized by high fever, evanescent rash, arthritis, and hyperferritinaemia. AOSD is also reported to be associated with other skin lesions, including persistent pruritic papules and plaques. This study aimed to assess the significance of dyskeratotic skin lesions in Japanese AOSD patients.We retrospectively assessed the histology of persistent pruritic skin lesions and evanescent rashes and the relationship between dyskeratotic cells, serum markers, and outcomes in 20 Japanese AOSD patients, comparing AOSD histology with that of dermatomyositis (DM), drug eruptions, and graft-versus-host disease (GVHD).As the results, Persistent pruritic lesions were characterized by scattered single keratinocytes with an apoptotic appearance confined to the upper layer of the epidermis and horny layer without inflammatory infiltrate. In contrast to AOSD, the histology of DM, drug eruption, and GVHD demonstrated dyskeratotic cells in all layers of the epidermis with inflammatory infiltrate. AOSD with evanescent rash showed no dyskeratotic cells. The dyskeratotic cells in pruritic AOSD lesions stained positive for ssDNA and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling, indicating apoptosis. Serum IL-18 was significantly higher in AOSD patients with dyskeratotic cells than those without, and generally required higher doses of glucocorticoids, immunosuppressants, and biologic agents. Two of ten AOSD patients with dyskeratotic cells died from hemophagocytic lymphohistiocytosis.In conclusion, Persistent pruritic AOSD skin lesions are characterized by dyskeratotic cells with apoptotic features, involving the upper layers of the epidermis. There may be a link to elevated IL-18. This dyskeratosis may be a negative prognostic indicator.
成人斯蒂尔病(AOSD)是一种全身性炎症性疾病,其特征为高热、一过性皮疹、关节炎和高铁蛋白血症。据报道,AOSD还与其他皮肤病变有关,包括持续性瘙痒性丘疹和斑块。本研究旨在评估日本AOSD患者中角化不良性皮肤病变的意义。我们回顾性评估了20例日本AOSD患者持续性瘙痒性皮肤病变和一过性皮疹的组织学,以及角化不良细胞、血清标志物与预后之间的关系,并将AOSD组织学与皮肌炎(DM)、药物疹和移植物抗宿主病(GVHD)的组织学进行比较。结果显示,持续性瘙痒性病变的特征是散在的单个角质形成细胞,具有凋亡外观,局限于表皮上层和角质层,无炎症浸润。与AOSD不同,DM、药物疹和GVHD的组织学显示表皮各层均有角化不良细胞,并伴有炎症浸润。有一过性皮疹的AOSD未显示角化不良细胞。瘙痒性AOSD病变中的角化不良细胞ssDNA和末端脱氧核苷酸转移酶介导的dUTP缺口末端标记染色呈阳性,表明存在凋亡。有角化不良细胞的AOSD患者血清IL-18显著高于无角化不良细胞的患者,且通常需要更高剂量的糖皮质激素、免疫抑制剂和生物制剂。10例有角化不良细胞的AOSD患者中有2例死于噬血细胞性淋巴组织细胞增生症。总之,持续性瘙痒性AOSD皮肤病变的特征是具有凋亡特征的角化不良细胞,累及表皮上层。可能与IL-18升高有关。这种角化不良可能是一个不良预后指标。