Familial complete pachydermoperiostosis presenting with vertebral hypertrophy and myelopathy

Abstract

Pachydermoperiostosis (PDP) is a rare, male-predominant (9:1) primary hypertrophic osteoarthropathy of the skin and bone, commonly called the acromegaly mimic. Clinical diagnosis of PDP is based on a triad of digital clubbing, pachydermia with coarse facial features, and radiographic evidence of long bone periostosis. It can manifest in a complete or incomplete form, with skin involvement distinguishing the complete subtype. The etiology of PDP remains uncertain, though it has been associated with pathogenic variants in genes involved in prostaglandin E2 metabolism genes (HPGD) in autosomal recessive primary hypertrophic osteoarthropathy-1 and SLCO2A1 in autosomal dominant primary hypertrophic osteoarthropathy. We present a 31-yr-old male with complete PDP with atypical clinical features of vertebral involvement, severe myelopathy and radiculopathy, mild digital clubbing, and frontal pachydermia. IGF-1 and HGH levels were normal despite the acromegalic features. Genetic testing did not identify variants in HPGD or SLCO2A1. The patient exhibited elevated bone-specific alkaline phosphatase levels and increased BMD, supporting the diagnosis of PDP. Iliac crest bone biopsies were technically difficult and contained only dense cortical bone. Dermatologic manifestations were managed with glycopyrrolate, dupilumab, and topical treatments. His bone disease was treated with intravenous bisphosphonates, yielding a marked decrease in bone-specific alkaline phosphatase levels. This case reveals the necessity of considering PDP in differential diagnoses for patients with atypical acromegalic features and highlights the potential for vertebral involvement in PDP, expanding the understanding of its clinical presentation.