Increased risk of rheumatoid arthritis among patients with endometriosis: a nationwide population-based cohort study

Xue, Yuhao; You, Liang-Tian; Ting, Hsin-Fu; Chen, Yu‐Wen; Sheng, Zi-Yun; Xie, Yi-Dong; Wang, Yu‐Hsun; Chiou, Jeng‐Yuan; Wei, James Cheng‐Chung

doi:10.1093/rheumatology/keaa784

Cited by 16 publications

(8 citation statements)

References 41 publications

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“…(2021), demonstrated an increased risk of SLE (adjusted HR= 2.37, 95% CI=1.35-4.14) compared to the non-endometriosis patients ( 27 ). In addition, another study suggested that women with endometriosis were significantly associated with rheumatoid arthritis ( 20 ). An immunological and inflammatory etiology has been speculated, as indicated by increased concentrations of activated macrophages, cytokines, T cells, and B cells ( 28 ).…”

Section: Discussionmentioning

confidence: 99%

“…Many studies suggest that women with endometriosis may have a hormonal imbalance and be prone to other immune surveillance-related imbalances such as suppressed cell-mediated immunity (high T, B, and NK cell counts, but lessened activity) and increased antibody-mediated immune response (high serum levels of immunoglobulin IgA, IgG, IgM, and anti-endometrial antibodies) ( 30 ). In addition, inflammatory cytokine concentrations like IL-1, IL-6, and TNF-α were elevated among endometriosis patients ( 20 ). Patients with endometriosis also present with other chronic inflammatory diseases, chronic inflammation, and increased oxidative stress ( 31 ).…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have revealed that autoimmune diseases such as Sjögren’s syndrome, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and inflammatory bowel disease were more prevalent in patients with endometriosis ( 19 ). Those with endometriosis are also more at risk of having rheumatoid arthritis, according to a retrospective cohort study ( 20 ). In a systematic review of 26 case-control cohort and cross-sectional studies, endometriosis was proposed to be related to autoimmune diseases, including Sjögren’s syndrome ( 21 ).…”

Section: Introductionmentioning

confidence: 99%

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Association Between Endometriosis and Subsequent Risk of Sjögren’s Syndrome: A Nationwide Population-Based Cohort Study

et al. 2022

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ObjectiveThe relationship between endometriosis and the ensuing risk of Sjögren’s syndrome has remained unclear. This study aims to present epidemiological evidence for this connection.MethodsThis is a retrospective cohort study of endometriosis patients (ICD-9-CM 617.0-617.9 and 621.3) and matched comparison group between 2000 and 2012 in the National Taiwan Insurance Research Database. After age matching, we analyzed the association between endometriosis and Sjögren’s syndrome (ICD-9-CM 710.2). We used the Cox proportional hazard model to examine the hazard ratio of incidental Sjögren’s syndrome. Subgroup analyses on age, comorbidities, and disease duration were also performed.ResultsA total of 73,665 individuals were included in this study. We identified 14733 newly diagnosed endometriosis patients and 58,932 non-endometriosis comparison group. The adjusted hazard ratio (HR) for incidental Sjögren’s syndrome was 1.45 (95% confidence interval CI=1.27-1.65) in the endometriosis group, compared to the non-endometriosis comparison group. In subgroup analysis, the adjusted HR was 1.53 (95% CI=1.25-1.88) in the age group of 20-39 and 1.41 (95% CI =1.18-1.68) in the age of 40-64. Time-vary analysis showed that endometriosis who have a follow-up time of fewer than five years (adjusted HR=1.57, 95% CI=1.32-1.87) have a significantly highest risk of having subsequent Sjögren’s syndrome.ConclusionThis population-based cohort study indicated that having a history of endometriosis puts patients at an increased risk of getting Sjögren’s syndrome afterward, especially in the age group of 20-39 and within the first five years after the diagnosis of endometriosis. Clinicians should recognize this possible association in managing endometriosis or Sjögren’s syndrome patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association Between Endometriosis and Subsequent Risk of Sjögren’s Syndrome: A Nationwide Population-Based Cohort Study

et al. 2022

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“…As we have discussed, the IL-23/Th17 axis is dysregulated in EMS, as well as various other chronic inflammatory diseases, including psoriasis, inflammatory bowel disease, rheumatoid arthritis, and multiple sclerosis [185,188,200,203,204]. The clinical presentation of these diseases alongside EMS has been extensively discussed [165,202,[205][206][207][208]. Here, we will focus on the current gaps in the literature, particularly on the possible pathophysiological pathways shared between EMS and its comorbidities in order to aid in the discovery of novel therapeutic targets.…”

Section: Immune-centered Comorbities May Share Common Pathological Me...mentioning

confidence: 96%

Endometriosis through an immunological lens: a pathophysiology based in immune dysregulation

et al. 2022

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Endometriosis (EMS) is an inflammatory, gynaecologic disease characterized by the growth of endometrial tissues outside the uterus. With no satisfactory therapies or non-invasive diagnostics available, a shift in perspectives on EMS pathophysiology is overdue. The implication of immune dysregulation in EMS pathogenesis and disease progression has been an evolving area of research, with numerous immune and inflammatory pathways identified. Traditional theories regarding the establishment of endometriotic lesions have lacked mechanistic explanations for their proliferation and survival until recent research unearthed the involvement of mesenchymal stem cell (MSC) and myeloid-derived suppressor cells (MDSCs) in a complex network of immune-endocrine signaling. The unique immunology of EMS is likely owing to estrogen dominance, as endocrine imbalance reliably cultivates immune dysregulation. Many of the phenomena observed in EMS parallel immune biology seen in various cancers, including accelerated somatic mutations in endometrial epithelial cells. Here, the high mutational load leads to EMS neoantigen development which potentially contributes to the lesion immune microenvironment. As well, EMS manifests comorbidity with several chronic inflammatory diseases that share common dysregulation of the interleukin-23 (IL-23)/IL-17 pathway (as seen in inflammatory bowel disease, psoriasis, and rheumatoid arthritis). EMS is especially relevant to the study of chronic pelvic pain (CPP) as 60% of EMS patients experience this symptom and chronic inflammation is believed to be central to the process of pain sensitization. Since the onset of the disease usually occurs in adolescence, and diagnosis only occurs years later once moderate to severe symptoms have developed, it is vital to innovate non-invasive diagnostic tools for earlier detection. Several potential biomarkers are being studied, including some cytokines, gene signatures, and extracellular vesicle (EV) signatures. By incorporating the immune perspectives of EMS into our research, approaches to diagnosis, and treatment solutions, the field has more promising avenues to clearly define EMS and offer patients relief.

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“…Another case-control study demonstrated an increasing number of immune-mediated conditions and co-occurring endometriosis [5]. A nationwide population-based study showed an increased risk of RA in patients with endometriosis during more than 10-year follow-up [6]. A population-based, retrospective cohort study from Taiwan including endometriosis (n = 16,758) and non-endometriosis (n = 16,758) women showed a significantly higher incidence rate in women with endometriosis (0.3 vs. 0.1 per 1,000 person-years) and hazard ratio (HR) for SLE [adjusted HR (aHR), 2.37; 95% confidence interval (CI) 1.35-4.14] as compared to the non-endometriosis group [7].…”

Section: Endometriosis and Autoimmune Diseasesmentioning

confidence: 99%

Endometriosis and autoimmunity

et al. 2022

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Endometriosis is an inflammatory oestrogen-dependent chronic disease and is mainly expressed by pain and increased infertility. Several studies showed an increased prevalence of autoimmune systemic diseases and various autoantibodies in endometriosis. The association of these autoimmune markers and diseases could raise the fact that endometriosis is an authentic autoimmune or inflammatory disease and thus could argue for the use of immunomodulatory therapies. Usually, it is considered that the autoantibodies did not directly act in endometrium implants growth, and could be rather implicated in endometriosis-related infertility. The use of immunomodulatory strategies could be an important alternative or additional strategy to the use of hormones and surgery but need prospective well-designed trials.

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Increased risk of rheumatoid arthritis among patients with endometriosis: a nationwide population-based cohort study

Cited by 16 publications

References 41 publications

Association Between Endometriosis and Subsequent Risk of Sjögren’s Syndrome: A Nationwide Population-Based Cohort Study

Association Between Endometriosis and Subsequent Risk of Sjögren’s Syndrome: A Nationwide Population-Based Cohort Study

Endometriosis through an immunological lens: a pathophysiology based in immune dysregulation

Endometriosis and autoimmunity

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