The first case of primary hypertrophic osteoarthropathy with soft tissue giant tumors caused by HPGD loss-of-function mutation.

Qianqian Pang,Xiaoping Xing,Weibo Xia,Yuping Xu,Ling Qin,Ou Wang,Mei Li,Yan Jiang,Xuan Qi

doi:10.1530/ec-19-0149

Abstract

BackgroundPrimary hypertrophic osteoarthropathy (PHO) is a rare genetic multi-organic disease characterized by digital clubbing, periostosis and pachydermia. Two genes, HPGD and SLCO2A1, which encodes 15-hydroxyprostaglandin dehydrogenase (15-PGDH) and prostaglandin transporter (PGT), respectively, have been reported to be related to PHO. Deficiency of aforementioned two genes leads to failure of prostaglandin E2 (PGE2) degradation and thereby elevated levels of PGE2. PGE2 plays an important role in tumorigenesis. Studies revealed a tumor suppressor activity of 15-PGDH in tumors, such as lung, bladder and breast cancers. However, to date, no HPGD-mutated PHO patients presenting concomitant tumor has been documented. In the present study, we reported the first case of HPGD-mutated PHO patient with soft tissue giant tumors at lower legs and evaluated the efficacy of selective COX-2 inhibitor (etoricoxib) treatment in the patient.MethodsIn this study, we summarized the clinical data, collected the serum and urine samples for biochemical test and analyzed the HPGD gene in our patient.ResultsA common HPGD mutation c.310_311delCT was identified in the patient. In addition to typical clinical features (digital clubbing, periostosis and pachydermia), the patient demonstrated a new clinical manifestation, a giant soft tissue tumor on the left lower leg which has not been reported in HPGD-mutated PHO patient before. After 6-month treatment with etoricoxib, the patient showed decreased PGE2 levels and improved PHO-related symptoms. Though the soft tissue tumor persisted, it seemed to be controlled under the etoricoxib treatment.ConclusionThis finding expanded the clinical spectrum of PHO and provided unique insights into the HPGD-mutated PHO.

Highlights

Primary hypertrophic osteoarthropathy (PHO; MIM 167100), known as pachydermoperiostosis or idiopathic hypertrophic osteoarthropathy, is a rare genetic multi-organic disease characterized by digital clubbing, periostosis and pachydermia
Both hydroxyprostaglandin dehydrogenase (HPGD) and SLCO2A1 deficiency can independently lead to failure of PGE2 degradation, resulting in elevated levels of prostaglandin E2 (PGE2) in the circulation, which is thought to contribute to the pathogenesis for PHO (1, 6)
PHO is a rare genetic disease featured by digital clubbing, periostosis, pachydermia and acro-osteolysis, which has been linked to the failure of prostaglandin metabolism

Summary

Introduction

Primary hypertrophic osteoarthropathy (PHO; MIM 167100), known as pachydermoperiostosis or idiopathic hypertrophic osteoarthropathy, is a rare genetic multi-organic disease characterized by digital clubbing, periostosis and pachydermia. Sefiert et al (7) revealed that manifestations of bones and joints found in patients with homozygous mutations in the HPGD, usually appear earlier than those in the SLCO2A1, suggesting the clinical heterogeneity between the two subtypes of PHO. We reported the first case of HPGD-mutated PHO patient with soft tissue giant tumors at lower legs and evaluated the efficacy of selective COX-2 inhibitor (etoricoxib) treatment in the patient. In addition to typical clinical features (digital clubbing, periostosis and pachydermia), the patient demonstrated a new clinical manifestation, a giant soft tissue tumor on the left lower leg which has not been reported in HPGD-mutated PHO patient before.

Methods

Results

Conclusion