Clinical, Biochemical, and Genetic Features of 41 Han Chinese Families With Primary Hypertrophic Osteoarthropathy, and Their Therapeutic Response to Etoricoxib: Results From a Six‐Month Prospective Clinical Intervention

ABSTRACT Primary hypertrophic osteoarthropathy (PHO) is a rare inherited disease caused by genetic defects in the prostaglandin metabolism pathway; disturbed prostaglandin E 2 (PGE 2 ) catabolism resulting in increased PGE 2 level is suggested in the pathogenesis. Forty‐three Han Chinese patients with PHO were studied and 41 of them were treated. Mutations in the HPGD gene, causing hypertrophic osteoarthropathy, primary, autosomal recessive 1 (PHOAR1; OMIM 259100), were identified in seven patients, and mutations in the SLCO2A1 gene, causing hypertrophic osteoarthropathy, primary, autosomal recessive 2 (PHOAR2; OMIM 614441), were identified in 36 patients. Clinical phenotypes of PHO varied, ranging from mild isolated finger clubbing to severe pachydermia and disabling joint swelling, even within families. Circulating PGE 2 metabolism features of PHOAR2 were different from those of PHOAR1. Different frequency and severity of pachydermia between the subgroups were also indicated. A percentage of PHOAR2 patients suffered from gastrointestinal hemorrhage, but this symptom was not observed in the PHOAR1 subgroup. Clinical evidence highlighted the essential role of sex hormones in prostaglandin transporter regulation with respect to PHOAR2 onset, although no significant associations of urinary PGE 2 or PGE‐M with sex hormones were identified. Treatment with etoricoxib, a selective cyclooxygenase‐2 inhibitor, was proved to be beneficial and safe. We detected its notable efficacy in decreasing urinary PGE 2 levels in the majority of the enrolled patients during 6 months of intervention; clinical phenotypes assessed, including pachydermia, finger clubbing, and joint swelling, were improved. We found no visible evidence of a positive effect of etoricoxib on periostosis; however, significant links between urinary PGE 2 and serum bone turnover markers indicated a potential role of decreased PGE 2 in periostosis management. This is the largest reported cohort of subjects genetically diagnosed with PHO. For the first time, we systematically investigated the biochemical and clinical differences between PHOAR1 and PHOAR2, and prospectively showed the positive efficacy and safety of etoricoxib for PHO patients. © 2017 American Society for Bone and Mineral Research.