Primary hypertrophic osteoarthropathy with digital clubbing and palmoplantar hyperhidrosis caused by 15-PGHD/HPGD loss-of-function mutations.

Digital clubbing is the most prominent feature in primary (PHO) and secondary (pulmonary) hypertrophic osteoarthropathy (HO). Homozygous and compound heterozygous germline mutations in the 15-hydroxyprostaglandin dehydrogenase (HPGD) gene encoding the major prostaglandin PGE2 catabolizing enzyme have been recently described in familial PHO cases. Elevated prostaglandin levels in affected individuals with cytokine-mediated tissue remodelling and vascular stimulation may underlie PHO and associated features as hyperhidrosis, acroosteolysis, pachyderma, periostosis and arthritis.