Clubbing of Fingers and Nails in Primary Hypertrophic Osteoarthropathy Type 1

A 37-year-old woman presented with a history, since childhood, of finger/toe and nail clubbing (Figure a), palmoplantar hyperkeratosis (Figure b) with hyperhidrosis and recurring arthritis. Ultrasound revealed chronic ankle arthritis, while X-ray findings included destroyed fingertips with fine distal interphalangeal joint structures and spicule-like periosteal outgrowths on the fibula and tibia. Chronic hypoxia due to lung/heart disease was ruled out as the most common cause of finger/toe and nail clubbing. Exome testing and analysis of genes associated with digital clubbing (n = 149) based on human phenotype ontology terminology (www.hpo.jax.org/) revealed a homozygous pathogenic HPGD variant consistent with parental consanguinity. HPGD codes for 15-hydroxyprostaglandin hydrogenase, which metabolizes prostaglandins. Autosomal recessive HPGD loss-of-function variants are causal for primary hypertrophic osteoarthropathy type 1, affecting primarily the skin and skeletal system. In addition to the mentioned symptoms, pachyderma, seborrhea, hirsutism, periostitis, anemia, and gastrointestinal abnormalities are also characteristic. No causal treatment is known. The differential diagnosis should include secondary hypertrophic osteoarthropathy due to internal diseases (in particular, heart failure and chronic obstructive pulmonary disease) or paraneoplastic syndrome as well as pseudoclubbing in secondary hyperparathyroidism.

Figure.