原发性肥厚性骨关节病(PHO)是一种与HPGD和SLCO2A1基因突变有关的罕见疾病。PHO的胃肠道受累更为罕见,其发病机制未知。PHO中胃肠道并发症的临床特征模拟其他基于自身免疫的肠道实体,如炎症性肠病和隐源性多灶性溃疡性狭窄性肠炎(CMUSE)。我们的目的是分析临床,遗传,中国PHO患者的放射学和病理学特征,并确定有和没有胃肠道受累的PHO患者之间的差异。
我们报告了2例胃肠道受累的PHO病例,并回顾了2000年1月1日至2018年4月30日发表的中国人群PHO的所有研究。分析了中国患者PHO的临床和遗传表现。我们比较了那些有胃肠道受累的患者与没有胃肠道受累的患者的特征。
这两名患者均为男性,具有完整形式的PHO超过10年。胃肠道相关症状包括腹泻,慢性消化道出血,不完全性肠梗阻,贫血,水肿,对依托考昔治疗没有反应。放射学检查显示肠段狭窄和肠壁增厚。内镜检查结果包括多发性溃疡和粘膜炎症。根据序列分析,两名患者均具有SLCO2A1突变。手术病理提示慢性炎症累及肠粘膜及粘膜下层,类似于CMUSE的组织学变化。根据对158例中国PHO患者的系统评价,17.2%有胃肠道受累,包括消化性溃疡,胃息肉,肥厚性胃炎,和节段性肠狭窄。胃肠道受累的患者更容易患贫血(40.0%vs.4.5%,P<0.001),低白蛋白血症(16.7%vs.0.9%,P=0.003),和骨髓纤维化(19.0%vs.0.9%,P=0.002)比那些没有。大多数胃肠道并发症患者有SLCO2A1突变(86.7%,13/15).
PHO患者消化道受累并不常见,常伴有贫血,肠道炎症导致低蛋白血症。肠道病理特征与克罗恩病不同,但与CMUSE相似。SLCO2A1的突变可能是PHO胃肠道受累的致病原因。NSAIDs对有胃肠道并发症的PHO患者可能无效。
Primary hypertrophic osteoarthropathy (PHO) is a rare disease related to HPGD and SLCO2A1 gene mutation. Gastrointestinal involvement of PHO is even rarer with unknown pathogenesis. Clinical features of GI complication in PHO mimics other auto-immune based bowel entities, such as inflammatory bowel diseases and cryptogenic multifocal ulcerous stenosing enteritis (CMUSE). We aimed to analyze the clinical, genetic, radiological and pathological features of Chinese patients with PHO and determine the difference between PHO patients presenting with and without GI involvement.
We reported two PHO cases with gastrointestinal involvement and reviewed all the studies of PHO in Chinese population published from January 1, 2000, to April 30, 2018. Clinical and genetic presentations of PHO in Chinese patients were analyzed. We compared the characteristics of those patients with gastrointestinal involvement against those without.
The two patients were both males with complete-form PHO for more than 10 years. GI related symptoms included diarrhea, chronic gastrointestinal hemorrhage, incomplete intestinal obstruction, anemia, and edema, which were unresponsive to etoricoxib treatment. Radiological examinations revealed segmental intestinal stenosis and thickened intestinal wall. Endoscopic findings included multiple ulcers and mucosal inflammation. Both patients had mutations of SLCO2A1 according to sequence analysis. The surgical pathology revealed chronic inflammation involving the intestinal mucosa and submucosa, similar to histological changes in CMUSE. According to the systemic
review of 158 Chinese patients with PHO, 17.2% had gastrointestinal involvement, including peptic ulcer, gastric polyps, hypertrophic gastritis, and segmental intestinal stenosis. Patients with gastrointestinal involvement were more likely to have anemia (40.0% vs. 4.5%, P < 0.001), hypoalbuminemia (16.7% vs. 0.9%, P = 0.003), and myelofibrosis (19.0% vs. 0.9%, P = 0.002) than those without. Most patients with gastrointestinal complication had SLCO2A1 mutation (86.7%, 13 /15).
Digestive tract involvement is uncommon in patients with PHO and often presents with anemia, and hypoalbuminemia resulted from intestinal inflammation. The intestinal pathologic characteristics are distinct from Crohn\'s disease but similar to CMUSE. Mutations in SLCO2A1 might be the pathogenic cause of GI involvement of PHO. NSAIDs may not be effective for PHO patients with gastrointestinal complications.