Acetaminophen as a possible treatment option for pachydermoperiostosis carrying mutated SLCO2A1: Case series

Pachydermoperiostosis (PDP) is a genetic disease characterized by digital clubbing, periostosis, and pachydermia. PDP with these three features, along with cutis verticis gyrata (CVG), is categorized as the "complete form," whereas cases without CVG are categorized as the "incomplete form." The condition is linked to elevated levels of systemic prostaglandin E2 (PGE2). About half of PDP patients experience arthralgia. The standard treatment for PDP is selective cyclooxygenase (COX)-2 inhibitors, but long-term usage can cause gastrointestinal side effects. Additionally, mutations in the SLCO2A1 can lead to chronic enteropathy associated with the SLCO2A1 gene (CEAS), making the use of selective COX-2 inhibitors particularly risky for PDP patients with CEAS. This has prompted the search for alternative treatments. In this study, five PDP patients-three with the complete form and two with the incomplete form-were treated with acetaminophen. The PGE-major urinary metabolite (PGE-MUM) was monitored as a biomarker of disease activity, reflecting systemic PGE2 levels. Before treatment, PGE-MUM levels were significantly elevated in patients with complete form and mildly elevated in those with incomplete form. Following acetaminophen, PGE-MUM levels decreased in patients with complete form, and all patients reported improvement in arthralgia without developing gastrointestinal symptoms. In conclusion, acetaminophen shows promise as an alternative treatment for PDP, effectively reducing PGE-MUM levels in certain patients and alleviating arthralgia while avoiding the gastrointestinal side effects associated with long-term COX-2 inhibitor usage.