与炎症性肠病患者的坏疽性脓皮病和结节性红斑相关的临床、血清学和遗传因素。
Clinical, serologic, and genetic factors associated with pyoderma gangrenosum and erythema nodosum in inflammatory bowel disease patients.
机构信息
*F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California; †Department of Pediatrics, Pediatric Inflammatory Bowel Disease Center, Cedars Sinai Medical Center, Los Angeles, California; ‡Meyerhoff Inflammatory Bowel Disease Center, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland; §Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland; ‖Department of Internal Medicine, Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut; ¶Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; **Universite de Montreal and the Montreal Heart Institute, Research Center, Montreal, Canada; ††Mount Sinai Inflammatory Bowel Disease Center, University of Toronto, Toronto, Canada; ‡‡Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, California; and §§Medical Genetics Research Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
出版信息
Inflamm Bowel Dis. 2014 Mar;20(3):525-33. doi: 10.1097/01.MIB.0000442011.60285.68.
BACKGROUND
Pyoderma gangrenosum (PG) and erythema nodosum (EN) are the most common cutaneous manifestations of inflammatory bowel disease (IBD) but little is known regarding their etiopathogenesis.
METHODS
We performed a case-control study comparing characteristics between IBD patients with a documented episode of PG (PG+) and/or EN (EN+) with those without PG (PG-) and EN (EN-). Data on clinical features were obtained by chart review. IBD-related serology was determined using enzyme-linked immunosorbent assay and genome-wide data generated using Illumina technology. Standard statistical tests for association were used.
RESULTS
We identified a total of 92 cases of PG and 103 cases of EN with genetic and clinical characteristics, of which 64 PG and 55 EN cases were available for serological analyses. Fewer male subjects were identified in the PG(+) (odds ratio 0.6, P = 0.009) and EN(+) groups (odds ratio 0.31, P = 0 < 0.0001). Colonic disease, previous IBD-related surgery, and noncutaneous extra-intestinal manifestations were more common among both PG(+) and EN(+) patients compared with controls. PG(+) was associated with anti-nuclear cytoplasmic antibody seropositivity (P = 0.03) and higher anti-nuclear cytoplasmic antibody level (P = 0.02) in Crohn's disease. Genetic associations with PG included known IBD loci (IL8RA [P = 0.00003] and PRDM1 [0.03]) as well as with USP15 (4.8 × 10) and TIMP3 (5.6 ×10). Genetic associations with EN included known IBD susceptibility genes (PTGER4 [P = 8.8 × 10], ITGAL [0.03]) as well as SOCS5 (9.64 × 10), CD207 (3.14 × 10), ITGB3 (7.56 × 10), and rs6828740 (4q26) (P < 5.0 × 10). Multivariable models using clinical, serologic, and genetic parameters predicted PG (area under the curve = 0.8) and EN (area under the curve = 0.97).
CONCLUSION
Cutaneous manifestations in IBD are associated with distinctive genetic characteristics and with the similar clinical characteristics, including the development of other extra-intestinal manifestations suggesting shared and distinct etiologies.
背景
坏疽性脓皮病（PG）和结节性红斑（EN）是炎症性肠病（IBD）最常见的皮肤表现，但对其病因发病机制知之甚少。
方法
我们进行了一项病例对照研究，比较了有记录的 PG（PG+）和/或 EN（EN+）发作的 IBD 患者与无 PG（PG-）和 EN（EN-）的患者之间的特征。通过病历回顾获取临床特征数据。使用酶联免疫吸附测定法测定与 IBD 相关的血清学，使用 Illumina 技术生成全基因组数据。使用标准统计检验进行关联分析。
结果
我们共确定了 92 例 PG 和 103 例 EN 的遗传和临床特征，其中 64 例 PG 和 55 例 EN 病例可进行血清学分析。PG（+）组（比值比 0.6，P = 0.009）和 EN（+）组（比值比 0.31，P < 0.0001）中男性患者较少。与对照组相比，PG（+）和 EN（+）患者中更常见的是结肠疾病、既往 IBD 相关手术和非皮肤肠外表现。PG（+）与克罗恩病中抗核细胞质抗体阳性（P = 0.03）和更高的抗核细胞质抗体水平（P = 0.02）相关。与 PG 相关的遗传关联包括已知的 IBD 位点（IL8RA [P = 0.00003] 和 PRDM1 [0.03]）以及 USP15（4.8×10）和 TIMP3（5.6×10）。与 EN 相关的遗传关联包括已知的 IBD 易感基因（PTGER4 [P = 8.8×10]、ITGAL [0.03]）以及 SOCS5（9.64×10）、CD207（3.14×10）、ITGB3（7.56×10）和 rs6828740（4q26）（P < 5.0×10）。使用临床、血清学和遗传参数的多变量模型预测 PG（曲线下面积 = 0.8）和 EN（曲线下面积 = 0.97）。
结论
IBD 的皮肤表现与独特的遗传特征以及相似的临床特征相关，包括其他肠外表现的发展，提示具有共同和独特的病因。
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