Risk of rheumatoid arthritis with endometriosis

The nationwide population-based cohort study from China enrolled

17,913 patients with endometriosis and 17,913 unaffected controls between 2000 and 2012. Participants were matched by age, index year and Charlson Comorbidity Index (CCI) score.

Patients were followed until the end of 2013 via Taiwan's National Health Insurance Research Database (NHIRD), at which time participants who developed RA were identified. The study’s maximum follow-up period was 13 years.

The National Health Insurance Program of Taiwan (NHIP) covers 23 million people in Taiwan and is one of the largest and most extensive population databases in the world, according to the authors, noting that NHIRD contains all insurance coverage claims data and relevant medical information for more than 99% of the population of Taiwan.

Patients with endometriosis were linked to an increased risk of incident RA compared to those without the disease, after adjusting for age, CCI score, and hormonal and surgical treatments: 3.56 vs. 1.30 per 10,000 person-years, for a hazard ratio (HR) of 3.71 (95% confidence interval [CI]: 2.91 to 5.73).

Among the adjusted variables, hormonal and surgical treatments were treated as time-dependent covariates.

Stratification analyses found similar risk associations that linked endometriosis to subsequent RA in all stratified age and CCI score subgroups: adjusted HR all >1, although not all were significant.

One plausible explanation for the increased risk of RA in patients with endometriosis is that with endometriosis, ectopic endometrial cells implant, grow and produce an inflammatory response, which can be expressed in the form of autoimmunity.

“Dysregulated autoimmune responses to ectopic endometrial tissues can create high levels of cytokines and then become systemic, which can lead to the development of RA,” wrote the authors.

Endometriosis and RA may also share a common etiology. The authors noted the possibility of a shared genetic etiology for the two diseases that has been linked to the PTPN22 gene and specific human leukocyte antigen (HLA) alleles; thus endometriosis can activate RA in vulnerable patients through shared genetic mechanisms.

Furthermore, stress is connected to the onset and exacerbation of RA. Chronic endometriosis-induced pain and disability, or other endometriosis consequences like infertility and sexual dysfunction, can transfer into stress and trigger the onset of RA.

The authors noted that the prevalence of RA in their study may be underestimated because only patients who sought medical help were enrolled. The relatively short observation period might also limit the likelihood of observing the occurrence of RA.

Still, the diagnosis of RA was from a rheumatologist and confirmed by a certificate of catastrophic illness, which improved the validity of the diagnosis.

Similarly, the number of endometriosis cases in the study may be underestimated because a gynecological ultrasound can never completely rule out the disease; for instance, superficial endometriosis cannot be detected by the technology, according to the authors.

To confirm the relationship between endometriosis and RA, additional prospective studies that account for genetic vulnerability and environmental exposures are justified, noted the authors.

Reference

1. Chen SF, Yang YC, Hsu CY, et al. Risk of rheumatoid arthritis in patients with endometriosis: a nationwide population-based cohort study. J Womens Health (Larchmt). 2021 Aug;30(8):1160-1164.

doi:10.1089/jwh.2020.8431