Yuan Lu, Liao Ruo-Xi, Lin Yuan-Yuan, Jiang Yan, Wang Ou, Li Mei, Xing Xiao-Ping, Pang Qian-Qian, Hsieh Evelyn, Xia Wei-Bo
Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Shuaifuyuan No. 1, Dongcheng District, Beijing 100730, China.
Section of Rheumatology, Department of Internal Medicine, Yale School of Medicine, P.O. Box 208031, New Haven, CT 06520, USA.
J Orthop Translat. 2018 Oct 31;18:109-118. doi: 10.1016/j.jot.2018.10.001. eCollection 2019 Jul.
Primary hypertrophic osteoarthropathy (PHO) is a rare disease involving joint, bone and skin. Two underlying genes responsible for this disease-hydroxyprostaglandin dehydrogenase () and solute carrier organic anion transporter family, member 2A1 ()-are both associated with aberrant accumulation of prostaglandin E2 (PGE2). Cyclooxygenase-2 (COX-2) is a key enzyme in PGE2 synthesis. This study was intended to evaluate the safety and efficacy of COX-2 inhibitor in the treatment of PHO.
We recruited patients presenting to Peking Union Medical Hospital between January 2009 and December 2016 who were diagnosed with PHO. Participants were given the COX-2 inhibitor etoricoxib (60 mg once daily) and followed up for 9 months. Gene analysis was performed at baseline. The following data were collected at baseline and during treatment: visual analogue score (VAS), volume of the distal middle finger (VDMF), knee joint circumference (KJC), serum and urinary levels of prostaglandin E2 (PGE2) and PGE metabolite (PGE-M) and serum levels of inflammatory markers.
A total of 27 patients were recruited, including seven patients with PHO type I (PHOAR1) carrying gene mutations and 20 patients with PHO type II (PHOAR2) carrying gene mutations. After treatment with etoricoxib, the majority of patients experienced resolution of symptoms including pachydermia (60.9%), joint swelling (100%), digital clubbing (74.1%) and hyperhidrosis (55.0%). In both the PHO subtypes, serum and urinary levels of PGE2 were elevated at baseline and declined sharply upon treatment. For PHOAR1 patients, serum and urinary PGE-M levels were relatively low and demonstrated minimal response to COX-2 inhibition. Among PHOAR2 patients, mean serum and urinary levels of PGE-M presented at a high level at baseline and were normalized after 3 months of treatment. No severe adverse effects were reported during the study period.
We found COX-2 inhibitor to be safe and effective for the treatment of PHO in our cohort.
The underlying genes responsible for PHO suggest COX inhibitor as potential therapy, and our study demonstrates the efficacy and safety of this treatment.
原发性肥大性骨关节病（PHO）是一种累及关节、骨骼和皮肤的罕见疾病。导致该疾病的两个潜在基因——羟基前列腺素脱氢酶（）和溶质载体有机阴离子转运体家族成员2A1（）——均与前列腺素E2（PGE2）的异常蓄积有关。环氧化酶-2（COX-2）是PGE2合成中的关键酶。本研究旨在评估COX-2抑制剂治疗PHO的安全性和有效性。
我们招募了2009年1月至2016年12月期间在北京协和医院就诊且被诊断为PHO的患者。参与者服用COX-2抑制剂依托考昔（每日一次，每次60毫克），并随访9个月。在基线时进行基因分析。在基线和治疗期间收集以下数据：视觉模拟评分（VAS）、中指远端体积（VDMF）、膝关节周长（KJC）、血清和尿液中前列腺素E2（PGE2）和PGE代谢物（PGE-M）的水平以及炎症标志物的血清水平。
共招募了27例患者，其中包括7例携带基因突变的I型PHO（PHOAR1）患者和20例携带基因突变的II型PHO（PHOAR2）患者。使用依托考昔治疗后，大多数患者的症状得到缓解，包括厚皮症（60.9%）、关节肿胀（100%）、杵状指（74.1%）和多汗症（55.0%）。在两种PHO亚型中，血清和尿液中PGE2的水平在基线时升高，治疗后急剧下降。对于PHOAR1患者，血清和尿液中PGE-M的水平相对较低，对COX-2抑制的反应最小。在PHOAR2患者中，血清和尿液中PGE-M的平均水平在基线时处于高水平，治疗3个月后恢复正常。在研究期间未报告严重不良反应。
我们发现COX-2抑制剂在我们的队列中治疗PHO是安全有效的。
导致PHO的潜在基因提示COX抑制剂作为潜在治疗方法，我们的研究证明了这种治疗方法的有效性和安全性。
