Am J Med Genet A. 2025 Jan 22:e64000. doi: 10.1002/ajmg.a.64000. Online ahead of print.
ABSTRACT
Primary Hypertrophic Osteoarthropathy (PHOAR1) is characterized by autosomal recessive loss of function variants in 15-hydroxyprostaglandin dehydrogenase (HPGD) leading to digital clubbing, periostosis, pachydermia, and severe hyperhidrosis. HPGD catalyzes the first step of prostaglandin E2 (PGE2) degradation. Selective COX-2 inhibitors have proved beneficial in adults, though it is unknown if early initiation of COX-2 inhibitors can alter the natural history of PHOAR1. This individual was diagnosed with PHOAR1 at 3.5 months of age due to homozygous HPGD c.218-1G>A variants. At presentation, she had a diffuse erythematous rash secondary to hyperhidrosis, mild symmetric clubbing of her fingertips, and mildly decreased mobility of her knees and wrists. By 20 months of age, she had more significant clubbing, mild flexion contractures, joint pain, and fatigue. She started celecoxib at 26 months of age. ResultsAfter 7 months of celecoxib, she had stable digital clubbing, improved hyperhidrosis and contractures, and resolution of her joint pain and fatigue. COX-2 inhibition appears to be a safe and effective intervention in young children with PHOAR1. More investigation is needed to assess safety and long-term impact on the natural history of PHOAR1 after COX-2 inhibition is initiated in early childhood.
PMID:39840454 | DOI:10.1002/ajmg.a.64000
