Hypertrophic Osteoarthropathy and Associated Enteropathies

Hypertrophic osteoarthropathy encompasses a spectrum of bone and joint changes characterised by digital clubbing, periostosis and arthralgia. In its primary form, genetic defects disrupt prostaglandin metabolism, leading to elevated levels of prostaglandin E2 that drive periosteal bone formation and soft-tissue swelling. Secondary forms arise in association with pulmonary, cardiac or hepatic disease. A rarer but increasingly recognised facet is the coexistence of enteropathic manifestations linked to mutations in the prostaglandin transporter gene SLCO2A1. These enteropathies present with chronic intestinal ulceration, hypoalbuminaemia and anaemia, and display histological features distinct from Crohn’s disease. Insights into pathogenic mechanisms have clarified the central role of prostaglandin dysregulation, offering targets for therapeutic intervention. Clinically, affected individuals may require multidisciplinary management, combining anti‐inflammatory agents, endoscopic surveillance and, in severe cases, surgical resection. The global significance of this condition lies in its demonstration of how systemic prostaglandin imbalance can produce both osteoarthropathic and gastrointestinal pathology, emphasising the need for integrated diagnostic and treatment strategies.

Research from Nature Portfolio

No recent Nature Portfolio content available.

Hypertrophic Osteoarthropathy and Associated Enteropathies publication trend

The graph below shows the total number of articles in hypertrophic osteoarthropathy and associated enteropathies across all publications each year (not limited to Nature Index journals).

Technical terms

Hypertrophic osteoarthropathy: syndrome of digital clubbing, periostosis and arthralgia driven by prostaglandin excess.

SLCO2A1: gene encoding the prostaglandin transporter responsible for cellular uptake and clearance of prostaglandin E2.

HPGD: gene encoding 15-hydroxyprostaglandin dehydrogenase, the principal enzyme for prostaglandin degradation.

Prostaglandin E2 (PGE2): lipid mediator involved in inflammation, bone remodelling and gastrointestinal mucosal integrity.

Periostosis: pathological new bone formation along the periosteal surface of long bones.

References

1. Primary hypertrophic osteoarthropathy: genetics, clinical features and management. Frontiers in Endocrinology (2023).
2. Clinical and genetic characteristics of Chinese patients diagnosed with chronic enteropathy associated with SLCO2A1 gene. Orphanet Journal of Rare Diseases (2024).
3. Clinical features of chronic enteropathy associated with SLCO2A1 gene: a new entity clinically distinct from Crohn’s disease. Journal of Gastroenterology (2018).
4. A Hereditary Enteropathy Caused by Mutations in the SLCO2A1 Gene, Encoding a Prostaglandin Transporter. PLOS Genetics (2015).