肥厚性皮膚骨膜症

PURPOSE: Primary hypertrophic osteoarthropathy (PHO) is a rare hereditary disorder characterized by both skin and skeletal abnormalities and is classified into two subtypes: PHO autosomal recessive 1 (PHOAR1) and PHO autosomal recessive 2 (PHOAR2). Cyclooxygenase-2 (COX-2) inhibitor Etoricoxib is first-line medication for PHO which could alleviate digital clubbing and pachydermia. However, its effects on the skeletal abnormalities associated with PHO remain unclear. This study aims to comprehensively investigate changes in bone microarchitecture at the distal radius, tibia and interphalangeal bones in PHO patients after 12-month Etoricoxib treatment. METHODS: A total of 20 PHO patients were enrolled, including 9 PHOAR1 patients and 11 PHOAR2 patients. Bone microstructure was investigated by high-resolution peripheral quantitative computed tomography (HR-pQCT). RESULTS: After 12 months' treatment, periosteosis in long bones and osteolysis at the 3rd interphalangeal joint of PHO were visually reduced. HR-pQCT parameters revealed improvements in total volumetric bone mineral density (Tot.vBMD), cortical vBMD (Ct.vBMD) at distal radius and tibia, accompanied with decreased cortical porosity. Trabecular bone showed no significant improvement. Besides, bone stiffness and failure load were significantly enhanced at radius site. In subgroup analysis, PHOAR2 patients experienced decline in trabecular number at the distal tibia, a change not observed in PHOAR1 patients. Correlation analysis revealed inverse associations between disease duration and changes in vBMD and bone strength in PHOAR2 patients, whereas no significant associations were found in PHOAR1 patients. CONCLUSIONS: Our findings indicated that 12 months of Etoricoxib treatment improved bone microstructure in PHO patients and highlighted differential treatment responses between different genotypes, which might optimize treatment strategies for PHO patients.

BACKGROUND: Primary hypertrophic osteoarthropathy (PHO) is a rare hereditary clinical syndrome characterized by digital clubbing, periostosis, and pachydermia. It is mainly caused by mutations in SLCO2A1 or HPGD, leading to impaired degradation and elevated levels of prostaglandin E2 (PGE2). In addition to the typical skeletal and skin manifestations, some patients may present with gastrointestinal or hematologic abnormalities, including anemia and myelofibrosis. This report describes a case of PHO with myelofibrosis and compound heterozygous SLCO2A1 mutations and review the literature. CASE REPORT: A 45-year-old man presented with a long history of severe fatigue and recurrent anemia accompanied by digital clubbing and skin thickening. Bone marrow biopsy revealed myelofibrosis, and imaging studies showed periostosis of the long bones. Given the anemia and gastrointestinal symptoms, differential diagnoses included Crohn's disease, intestinal tuberculosis, and other hematologic disorders associated with myelofibrosis, which were excluded by endoscopic and hematologic evaluations. Whole-exome sequencing revealed that the patient carried compound heterozygous variants in SLCO2A1 (c.940 + 1G>A and c.440G>A/p.Trp147*), confirming the diagnosis of PHO. Family investigation showed that his parents and offspring were all asymptomatic carriers with one heterozygous variant, which is consistent with autosomal recessive inheritance. CONCLUSION: Myelofibrosis is a rare but important complication of PHO and may be more frequent in patients with biallelic SLCO2A1 variants. Genetic testing and hematologic evaluation in PHO patients can help with early identification of related complications.

Primary Hypertrophic Osteoarthropathy (PHO) demonstrates variable inherited penetrance, and clinical expression. The identification of SLCO2A1 (solute carrier organic anion transporter family member 2A1), HPGD(Hydroxyl prostaglandin dehydrogenase) has provided new insights into its pathophysiology. These discoveries have facilitated diagnosis, particularly in paediatric population. This study emphasises genetic level diagnostic approach alongside therapeutic interventions. A prospective, multicentric study was conducted at two tertiary care centre. Eight PHO cases were identified after excluding all other causes of transfusion-dependent microcytic hypochromic anaemia. Genetic mutation in the genes SLCO2A1, HPGD were studied. All patients received treatment with etoricoxib and steroid therapy, were followed up for one year. In our cohort, all were males. Six patients had classical phenotypic expression. Three had prominent gastrointestinal manifestations. Two paediatric patients had family history of transfusion-dependent anaemia. All had homozygous recessive SLCO2A1 mutation. Five patients experienced transient improvement in form of transfusion-free period, decrease in spleen size, and reduced arthralgia, fatigue. Three patients didn't demonstrate any major therapeutic benefit. Clinicians should maintain high index of suspicion for PHO in young patients presenting with transfusion-dependent microcytic anaemia, particularly after excluding all inherited, acquired causes. Although etoricoxib, steroids show therapeutic promise. Further extensive research is necessary to establish their efficacy, safety.