In honor of Autoimmune Arthritis Day on 5/20, I wanted to touch on an article that was recently published about the association between Rheumatoid Arthritis (RA) and Parkinson’s disease (PD).
On May 1, 2023, Jihun Kan and colleagues published a study including nearly 55,000 Korean patients stating that those with RA had a 1.74-fold higher risk of PD compared to those people without RA. In addition, patients with “seropositive” RA had a higher risk than those with “seronegative” RA. Seropositive means that their blood had detectable antibodies that could attack their body (autoimmune) and cause joint inflammation. Seronegative means those autoimmune antibodies are not present but the patient still has other evidence of RA. There have been other studies that have shown similar outcomes linking RA with increased risk of PD in other populations, such as in this study in Taiwan.
However, there are also multiple studies that show that the incidence of PD is actually lower in those with RA in populations from Finland, Sweden, China, and Taiwan (in contrast to the above study in Taiwan!) or that there is no relationship as reported in a Danish population.
Why would PD and RA even be related? We know that inflammation is involved in the neurodegeneration seen in PD and is also the key contributor in RA. Additionally, there is SOME evidence that certain anti-inflammatory medications, including some to specifically treat RA (disease modifying antirheumatic drugs or DMARDs), may lower the risk of PD. In the aforementioned Swedish study, Paakinaho and colleagues showed that chloroquine/hydroxychloroquine lowered the risk of PD but other DMARDs such as sulfasalazine, methotrexate, gold preparations, and immunosuppressants were NOT associated with any change in PD risk.
So what does it all mean and who is right? It’s difficult to say for sure. It’s important to understand that associations are just that - associations. They do not necessarily imply causation. There are likely numerous factors that contribute to the risk of PD and RA including genetic causes and predispositions, environmental exposures, tobacco use, diets, and other stressors that, together, determine overall risk of any disease. Some of these risk factors are likely shared between the two diseases. Perhaps certain genetic risk factors are more or less common in certain regions or varying diets change gut microbiomes in one region of the world or country versus another. Maybe it’s the severity of RA (which in turn helps dictate which medications are tried) that changes the association one way or another. One thing we do know is there is not yet a clear, consistent relationship that has been identified and more work needs to be done to understand what the true association between PD and RA is, if any.
As always, feel free to reach out to us at Synapticure with any questions or concerns.
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- Bacelis J, Compagno M, George S, Pospisilik JA, Brundin P, Naluai ÅT, Brundin L. Decreased Risk of Parkinson's Disease After Rheumatoid Arthritis Diagnosis: A Nested Case-Control Study with Matched Cases and Controls. J Parkinsons Dis. 2021;11(2):821-832. doi: 10.3233/JPD-202418. PMID: 33682730; PMCID: PMC8150472.
- Castillo-Rangel C, Marin G, Hernández-Contreras KA, Vichi-Ramírez MM, Zarate-Calderon C, Torres-Pineda O, Diaz-Chiguer DL, De la Mora González D, Gómez Apo E, Teco-Cortes JA, Santos-Paez FM, Coello-Torres MLÁ, Baldoncini M, Reyes Soto G, Aranda-Abreu GE, García LI. Neuroinflammation in Parkinson's Disease: From Gene to Clinic: A Systematic Review. Int J Mol Sci. 2023 Mar 17;24(6):5792. doi: 10.3390/ijms24065792. PMID: 36982866; PMCID: PMC10051221.
- Chang CC, Lin TM, Chang YS, Chen WS, Sheu JJ, Chen YH, Chen JH. Autoimmune rheumatic diseases and the risk of Parkinson disease: a nationwide population-based cohort study in Taiwan. Ann Med. 2018 Feb;50(1):83-90. doi: 10.1080/07853890.2017.1412088. Epub 2017 Dec 20. PMID: 29224375.
- Kang J, Eun Y, Jang W, Cho MH, Han K, Jung J, Kim Y, Kim GT, Shin DW, Kim H. Rheumatoid Arthritis and Risk of Parkinson Disease in Korea. JAMA Neurol. 2023 May 1:e230932. doi: 10.1001/jamaneurol.2023.0932. Epub ahead of print. PMID: 37126341; PMCID: PMC10152376.
- Li C, Ou R, Shang H. Rheumatoid arthritis decreases risk for Parkinson's disease: a Mendelian randomization study. NPJ Parkinsons Dis. 2021 Mar 2;7(1):17. doi: 10.1038/s41531-021-00166-x. PMID: 33654087; PMCID: PMC7925660.
- Paakinaho A, Koponen M, Tiihonen M, Kauppi M, Hartikainen S, Tolppanen AM. Disease-Modifying Antirheumatic Drugs and Risk of Parkinson Disease: Nested Case-Control Study of People With Rheumatoid Arthritis. Neurology. 2022 Mar 22;98(12):e1273-e1281. doi: 10.1212/WNL.0000000000013303. Epub 2022 Jan 21. PMID: 35064025; PMCID: PMC8967329.
- Rugbjerg K, Friis S, Ritz B, Schernhammer ES, Korbo L, Olsen JH. Autoimmune disease and risk for Parkinson disease: a population-based case-control study. Neurology. 2009 Nov 3;73(18):1462-8. doi: 10.1212/WNL.0b013e3181c06635. Epub 2009 Sep 23. PMID: 19776374; PMCID: PMC2779008.
- Sung YF, Liu FC, Lin CC, Lee JT, Yang FC, Chou YC, Lin CL, Kao CH, Lo HY, Yang TY. Reduced Risk of Parkinson Disease in Patients With Rheumatoid Arthritis: A Nationwide Population-Based Study. Mayo Clin Proc. 2016 Oct;91(10):1346-1353. doi: 10.1016/j.mayocp.2016.06.023. PMID: 27712633.