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Abstract
Objectives Little is known about relevant events in the at-risk phase of rheumatoid arthritis before the development of clinically apparent inflammatory arthritis (IA). The present study assessed musculoskeletal symptoms, infections and comorbidity in future IA patients.
Methods In a nested case–control study using electronic health records of general practitioners, the frequency and timing of 192 symptoms or diseases were evaluated before a diagnosis of IA, using the International Classification of Primary Care coding system. Cases were 2314 adults with a new diagnosis IA between 2012 and 2016; controls were matched 1:2. The frequency of primary care visits was compared using logistic regression.
Results The frequency of visits for musculoskeletal symptoms (mostly of shoulders, wrists, fingers and knees) and carpal tunnel syndrome was significantly higher in IA patients vs controls within the final 1.5 years before diagnosis, with ORs of 3.2 (95% CI 2.8 to 3.5), 2.8 (95% CI 2.5 to 3.1) and 2.5 (95% CI 2.2 to 2.8) at 6, 12 and 18 months before diagnosis, respectively. Also, infections (notably of the genital and urinary tracts), IA-comorbidities and chronic diseases were more prevalent in cases than controls, but more evenly spread out over the whole 6-year period before IA. A decision tree was created including all symptoms and diseases.
Conclusion There was an increased frequency of primary care visits for musculoskeletal symptoms, infections and comorbidities prior to the diagnosis of IA. This diverging trend is present for 4–6 years, but becomes statistically significant 1.5 years before the diagnosis. Validation of these results is warranted.
- Autoantibodies
- Rheumatoid Arthritis
- Inflammation
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Footnotes
Contributors Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work: MvB-T, MMJN, JWRT, JK, DvS, all authors contributed to the acquisition of the data. Drafting the work or revising it critically for important intellectual content: MvB-T, MMJN, JK, DvS. Final approval of the version to be published: all authors. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved: all author.
Funding This manuscript was included in a PhD thesis which can be found in UvA repository (URL: https://pure.uva.nl/ws/files/38672232/Thesis.pdf, chapter 6).
Competing interests None declared.
Patient consent for publication Not required.
Ethical approval information The study was approved according to the governance code of Nivel-PCD, under number NZR-00314.045. Dutch law allows the use of EHRs for research purposes under certain conditions. According to this legislation, obtaining informed consent nor approval by a medical ethics committee are obligatory for this type of observational studies containing no directly identifiable data (Dutch Civil Law, Article 7:458).
Data sharing statement Data can be shared by the authors on reasonable request.
Provenance and peer review Not commissioned; externally peer reviewed.