Department of Dermatology, School of Medicine, The Johns Hopkins University, Baltimore, Maryland, USA.
Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts, USA; Department of Biomedical Informatics, Harvard Medical School, Boston, Massachusetts, USA.
J Invest Dermatol. 2022 May;142(5):1300-1308.e3. doi: 10.1016/j.jid.2021.10.011. Epub 2021 Oct 27.
Patients with prurigo nodularis (PN) suffer from intractable itch and dramatic reduction in QOL. Although there is significant clinical heterogeneity in the presentation of PN, disease endotypes remain unknown. We assayed circulating plasma cytokine concentrations in patients with PN (n = 20) along with matched healthy controls and utilized an unsupervised machine learning algorithm to identify disease endotypes. We found two distinct clusters of patients with PN with noninflammatory (cluster 1) and inflammatory (cluster 2) plasma profiles. Cluster 2 had more African Americans (82%, n = 9 vs. 33%, n = 3; P = 0.028), higher Worst Itch Numeric Rating Scale scores (9.5 ± 0.9 vs. 8.3 ± 1.2; P = 0.036), and lower QOL as reflected by higher Dermatology Life Quality Index scores (21.9 ± 6.4 vs. 13.0 ± 4.1; P = 0.015). In addition, cluster 1 had a higher rate of myelopathy (67%, n = 6 vs. 18%, n = 2; P = 0.028). Compared with cluster 1, cluster 2 had higher levels of IL-1α, IL-4, IL-5, IL-6, IL-10, IL-17A, IL-22, IL-25, and IFN-α. With population-level analysis, African American patients with PN had higher erythrocyte sedimentation rate, C-reactive protein, ferritin, and eosinophils and lower transferrin than Caucasian patients with PN. These findings indicate discrete clusters of patients with PN with plasma biomarker profiles corresponding to distinct demographic and clinical characteristics, potentially allowing for precision medicine approaches to treat PN.
结节性痒疹（PN）患者饱受剧烈瘙痒和生活质量严重下降之苦。尽管 PN 临床表现存在显著的临床异质性，但疾病内型仍不清楚。我们检测了 20 例 PN 患者和匹配的健康对照者的循环血浆细胞因子浓度，并利用无监督机器学习算法来识别疾病内型。我们发现 PN 患者存在两个截然不同的亚群，具有非炎症性（亚群 1）和炎症性（亚群 2）的血浆特征。亚群 2中非裔美国人更多（82%，n=9 比 33%，n=3；P=0.028），Worst Itch Numeric Rating Scale 评分更高（9.5±0.9 比 8.3±1.2；P=0.036），生活质量更低，反映在更高的皮肤病生活质量指数评分（21.9±6.4 比 13.0±4.1；P=0.015）。此外，亚群 1的脊髓病发生率更高（67%，n=6 比 18%，n=2；P=0.028）。与亚群 1相比，亚群 2的 IL-1α、IL-4、IL-5、IL-6、IL-10、IL-17A、IL-22、IL-25 和 IFN-α水平更高。通过人群水平分析，PN 非裔美国患者的红细胞沉降率、C 反应蛋白、铁蛋白和嗜酸性粒细胞更高，转铁蛋白更低，而 PN 白种患者则更低。这些发现表明 PN 患者存在不同的亚群，其血浆生物标志物谱与不同的人口统计学和临床特征相对应，可能为治疗 PN 提供精准医学方法。
