To evaluate the characteristics of NXG and propose diagnostic criteria.
This multicenter cross-sectional study was conducted at tertiary academic referral centers and followed by a systematic review and a consensus exercise. The multicenter cohort included patients with NXG diagnosed at the Brigham and Women\'s and Massachusetts General Hospitals (2000-2018), the University of Iowa Hospitals and Clinics (2000-2018), and the University of Pennsylvania Health System (2008-2018). The systematic review was conducted in 2018 and included patients with NXG identified in the Cochrane, Ovid EMBASE, PubMed, and Web of Science databases. The consensus exercise was conducted by 8 board-certified dermatologists to identify diagnostic criteria.
Demographic factors, comorbidities, clinical features, and treatment response.
Of 235 included patients with NXG (34 from the multicenter cohort and 201 from the systematic review results), the mean (SD) age at presentation was 61.6 (14.2) years; 147 (62.6%) were female. Paraproteinemia was detected in 193 patients (82.1%), most often IgG-κ (117 patients [50.0%]). A malignant condition was detected in 59 patients (25.1%), most often multiple myeloma (33 patients [14.0%]). The overall rate of paraproteinemia and/or a malignant condition was 83.8% (197 patients). In the multicenter cohort, evolution of paraproteinemia into multiple myeloma was observed up to 5.7 years (median [range], 2.4 [0.1-5.7] years) after NXG presentation. Cutaneous lesions consisted of papules, plaques, and/or nodules, typically yellow or orange in color (113 of 187 [60.4%]) with a periorbital distribution (130 of 219 [59.3%]). The eye was the leading site of extracutaneous involvement (34 of 235 [14.5%]). In the multicenter cohort, intravenous immunoglobulin had the best treatment response rate (9 of 9 patients [100%]), followed by antimalarial drugs (4 of 5 patients [80%]), intralesional triamcinolone (6 of 8 patients [75%]), surgery (3 of 4 patients [75%]), chemotherapy (8 of 12 patients [67%]), and lenalidomide or thalidomide (5 of 8 patients [63%]). The consensus exercise yielded 2 major criteria, which were (1) clinical and (2) histopathological features consistent with NXG, and 2 minor criteria, consisting of (1) paraproteinemia, plasma-cell dyscrasia, and/or other associated lymphoproliferative disorder and (2) periorbital distribution of cutaneous lesions. In the absence of foreign body, infection, or another identifiable cause, fulfillment of both major and at least 1 minor criterion were proposed to establish the diagnosis of NXG.
Necrobiotic xanthogranuloma is a multisystem disorder associated with paraproteinemia and malignant conditions. The proposed diagnostic criteria may advance clinical research and should be validated.
评估NXG的特征并提出诊断标准。
这项多中心横断面研究是在高等学术转诊中心进行的,随后进行了系统评价和共识练习。多中心队列包括在布莱根妇女医院和马萨诸塞州综合医院(2000-2018)诊断为NXG的患者,爱荷华大学医院和诊所(2000-2018),和宾夕法尼亚大学卫生系统(2008-2018)。系统评价于2018年进行,包括在Cochrane中确定的NXG患者,OvidEmbase,PubMed,和WebofScience数据库。8位经过委员会认证的皮肤科医生进行了共识练习,以确定诊断标准。
人口因素,合并症,临床特征,和治疗反应。
在纳入的235名NXG患者中(34名来自多中心队列,201名来自系统回顾结果),报告时的平均(SD)年龄为61.6(14.2)岁;147岁(62.6%)为女性.在193例患者中检测到副蛋白血症(82.1%),最常见的IgG-κ(117例[50.0%])。59例(25.1%)患者出现恶性肿瘤,最常见的多发性骨髓瘤(33例[14.0%])。副蛋白血症和/或恶性疾病的总发生率为83.8%(197例患者)。在多中心队列中,观察到副蛋白血症演变为多发性骨髓瘤长达5.7年(中位数[范围],2.4[0.1-5.7]年)在NXG演示后。皮肤病变包括丘疹,斑块,和/或结节,通常为黄色或橙色(187[60.4%]中的113个),具有轨道周围分布(219[59.3%]中的130个)。眼睛是皮外受累的主要部位(235个中的34个[14.5%])。在多中心队列中,静脉注射免疫球蛋白有最好的治疗反应率(9例患者中的9例[100%]),其次是抗疟药(5名患者中有4名[80%]),病灶内曲安西龙(8例患者中的6例[75%]),手术(4例患者中的3例[75%]),化疗(12例患者中有8例[67%]),和来那度胺或沙利度胺(8例患者中的5例[63%])。共识工作产生了两个主要标准,(1)临床和(2)与NXG一致的组织病理学特征,和两个次要标准,包括(1)副蛋白血症,浆细胞发育不良,和/或其他相关的淋巴增生性疾病和(2)皮肤病变的眶周分布。在没有异物的情况下,感染,或其他可识别的原因,提出了同时满足主要和至少1个次要标准来建立NXG的诊断。
坏死生物黄色肉芽肿是一种与副蛋白血症和恶性疾病相关的多系统疾病。拟议的诊断标准可能会促进临床研究,应予以验证。