Abstract
Objective
The purpose of this retrospective cohort study was to characterize the prevalence, incidence, associated conditions, and demographics of complex regional pain syndrome (CRPS) using a large, real-world dataset.Methods
This retrospective cohort study analyzed data from the TriNetX Global Collaborative Network, including over 150 million patients across 18 countries, to identify CRPS prevalence, incidence, demographics, and comorbidities.Results
A total of 99,878 patients with CRPS were identified over a 20-year period, based on ICD-10-coded electronic health record data. Overall prevalence was 62 per 100,000 individuals, and incidence was 13.5 per 100,000 person-years, with rates more than twice as high in females compared to males. Both measures peaked in individuals aged 40-44 years and were highest among Native Hawaiians/Pacific Islanders. Lower extremity involvement was 1.5 times more common than upper extremity involvement, and cumulative incidence was noticeably higher following fractures, particularly foot fractures (495 per 100,000). Rates of CRPS more than doubled from 2004-2008 to 2019-2023. Bidirectional associations were observed between CRPS and multiple conditions, including depression, anxiety, insomnia, and irritable bowel syndrome, with relative risks ranging from approximately 1.4-fold to 24-fold.Discussion
Using one of the largest CRPS cohorts reported to date, this real-world analysis clarifies contemporary epidemiology and reveals bidirectional associations with psychological, inflammatory, and autoimmune conditions. The findings are consistent with a multifactorial clinical profile involving immune, neurologic, and psychosocial mechanisms, guiding future mechanistic and clinical research.