■原发性肥厚性骨关节病(PHO)是一种罕见的疾病,涉及关节,骨头和皮肤。负责这种疾病的两个潜在基因-羟基前列腺素脱氢酶(HPGD)和溶质载体有机阴离子转运蛋白家族,成员2A1(SLCO2A1)-均与前列腺素E2(PGE2)的异常积累有关。环氧合酶-2(COX-2)是PGE2合成的关键酶。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月期间到北京协和医院就诊并被诊断为PHO的患者。给予COX-2抑制剂依托考昔(60mg,每日一次),随访9个月。在基线进行基因分析。在基线和治疗期间收集以下数据:视觉模拟评分(VAS),远端中指的体积(VDMF),膝关节围(KJC),血清和尿液中前列腺素E2(PGE2)和PGE代谢物(PGE-M)的水平以及血清炎症标志物的水平。
■共招募了27名患者,包括7例携带HPGD基因突变的PHOI型(PHOAR1)患者和20例携带SLCO2A1基因突变的PHOII型(PHOAR2)患者。用依托考昔治疗后,大多数患者经历了症状的缓解,包括厚皮症(60.9%),关节肿胀(100%),数字俱乐部(74.1%)和多汗症(55.0%)。在这两种PHO亚型中,血清和尿中PGE2水平在基线时升高,治疗后急剧下降.对于PHOAR1患者,血清和尿PGE-M水平相对较低,对COX-2抑制反应最小.在PHOAR2患者中,PGE-M的平均血清和尿水平在基线时呈现高水平,治疗3个月后恢复正常.在研究期间没有报告严重的不良反应。
■在我们的队列中,我们发现COX-2抑制剂对于治疗PHO是安全有效的。
■导致PHO的潜在基因表明COX抑制剂是潜在的治疗方法,我们的研究证明了这种治疗的有效性和安全性.
UNASSIGNED: Primary hypertrophic osteoarthropathy (PHO) is a rare disease involving joint, bone and skin. Two underlying genes responsible for this disease-hydroxyprostaglandin dehydrogenase (HPGD) and solute carrier organic anion transporter family, member 2A1 (SLCO2A1)-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.
UNASSIGNED: 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.
UNASSIGNED: A total of 27 patients were recruited, including seven patients with PHO type I (PHOAR1) carrying HPGD gene mutations and 20 patients with PHO type II (PHOAR2) carrying SLCO2A1 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.
UNASSIGNED: We found COX-2 inhibitor to be safe and effective for the treatment of PHO in our cohort.
UNASSIGNED: The underlying genes responsible for PHO suggest COX inhibitor as potential therapy, and our
study demonstrates the efficacy and safety of this treatment.