Author: Nicholas Jo
Rheumatoid arthritis (RA) is the most prevalent form of the disease affecting joints, muscles, and tendons (Schneider & Krüger, 2013). Early diagnosis and recognition of signs and symptoms prevent irreversible joint damage (Aletaha & Smolen, 2018).
Rheumatoid arthritis is caused when the connective tissue that lines most cavity joints becomes inflamed (Aletaha & Smolen, 2018). Inflammation compromises bones as well as cartilage-bone junctions, which causes pain and mobility issues (Aletaha & Smolen, 2018). If left untreated, Rheumatoid arthritis heavily impacts an individual’s quality of life and the ability to function normally in 80% of patients (Aletaha & Smolen, 2018).
Epidemiological studies have reported the highest prevalence rates of rheumatoid arthritis in the United Kingdom and the United States, at 471 per 100000 individuals and 375-400 per 100000 individuals, respectively (Safiri et al., 2019). The lowest rates of rheumatoid arthritis prevalence are at 90 individuals per 100000 in West African and East Asian regions (Safiri et al., 2019). Sex-specific incidence of rheumatoid arthritis between 2005-2014 suggests a rate of 51 per 100000 women and 29 per 100000 men, denoting the higher occurrence of the disease in women as opposed to men (Myasoedova et al., 2020).
The peak age-specific incidence rate is reportedly at approximately 50 years of age (Safiri et al., 2019; van der Woude & van der Helm-van Mil, 2018). Further, peak rates of rheumatoid arthritis prevalence have been reported between 60 to 70 years of age globally (Safiri et al., 2019).
Rheumatoid arthritis is an autoimmune chronic inflammatory disorder of multiple joints, typically those of the hands and the feet (McInnes & Schett, 2007). Pathogenesis of RA is associated with two autoimmune antibodies, rheumatoid factor (RF), which reacts against the Fc component of antibodies (Firestein, 2003), and the anti-cyclic citrullinated peptide antibody (ACPA), which targets citrullinated self-proteins (McInnes & Schett, 2007).
Rheumatoid factor is suggested to produce immune complexes with its targets, leading to complement activation and neutrophil recruitment which mediate damage to synovial tissue (Firestein, 2003). Anti-cyclic citrullinated peptide antibodies are developed against citrullinated proteins in the synovial fluid through unknown mechanisms, though suggested pathways involve hypercitrullination or citrullination of proteins at unusual amino acids, giving rise to foreign epitopes against which an immune response may be initiated (Darrah & Andrade, 2018).
Alongside autoantibodies, genetic polymorphism in the HLA-DR subtype of MHC Class II complexes leads to T cell receptor (TCR) stimulation with self-epitopes, constituting T cell activation (Smolen et al., 2016). Resident macrophages and cells of the synovium produce cytokines (TGFβ, IL-12, IL-6) that lead to the activation and differentiation of CD4+ T cells into TH1 and TH17 effectors (as studied in animal models in vivo) that via paracrine stimulation of leukocytes, B cells, and CD8+ cytotoxic T cells cause the joint erosion and persistent inflammation characteristic of RA (McInnes & Schett, 2007).
- Pain and swelling of joints in hand and feet (Schneider & Krüger, 2013)
- Joint inflammation has a direct association with rheumatoid arthritis
- Degradation of cartilage and bone
- Morning stiffness lasting more than 30minutes
- Tendon inflammation
(Aletaha & Smolen, 2018)
- Physical stress
- Recurrent joint stiffness
- Any trauma to the joint
- Age over 50 years old (Safiri et al.,2019)
- Genetic factors such as the gene for HLA-DRB1
(Schneider & Krüger, 2013)
Inflammation and bone loss in more than two joints are a clear indication of RA (Schneider & Krüger, 2013). Inflammation can then be measured via a specific type of sonography called doppler sonography, which can give information regarding inflammation in the joint (Aletaha & Smolen, 2018). Radiography can also be used to detect bone loss in joints and can present additional information to diagnose the individual with RA (Aletaha & Smolen, 2018).
Blood tests can also be conducted to test for increased concentrations of C-reactive protein (CRP), increased erythrocyte sedimentation rate (ESR), as well as the presence of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) (Schneider & Krüger, 2013). Furthermore, the ACR/EULAR 2010 classification criteria, which use a point system assigned to factors such as joint distribution, size, and common RA symptoms, are utilized to confirm the correct diagnosis (Schneider & Krüger, 2013).
The first line of treatment against RA would be the prescription of disease-modifying drugs (DMARDs) such as methotrexate (Schneider & Krüger, 2013). The recommended prescription is 25mg weekly alongside glucocorticoids and is effective in 40-50% of patients (Aletaha & Smolen, 2018). Disease-modifying drugs suppress disease suppression, and their effectiveness has been highlighted in studies whereby they reverse the loss of function in over 80% of patients if administered within six months of diagnosis (Schneider & Krüger, 2013).
Physical function and exercise with a physiotherapist are also suggested for patients with RA (Schneider & Krüger, 2013). Individualized fitness programs which go over dynamic exercises and focus on strength and endurance training helps patients cope with some of the debilitating effects of RA (Schneider & Krüger, 2013). Alongside physical and medical treatment, Schneider & Krüger suggests a psychological intervention (Schneider & Krüger, 2013). It is observed that recently diagnosed patients are overwhelmed by the amount of new information provided, and endure a significant amount of stress when deciding treatment options (Schneider & Krüger, 2013).
Articles on Misdiagnosis
Devaraj, N. K. (2019). The Atypical Presentation of Rheumatoid Arthritis in an Elderly Woman: A Case Report. Ethiopian Journal of Health Sciences, 29(1), 957–958. DOI:10.4314/ejhs.v29i1.18
Glaser, C., Rieg, S., Wiech, T., Scholz, C., Endres, D., Stich, O., Hasselblatt, P., Geißdörfer, W., Bogdan, C., Serr, A., Häcker, G., Voll, R. E., Thiel, J., & Venhoff, N. (2017). Whipple’s disease mimicking rheumatoid arthritis can cause misdiagnosis and treatment failure. Orphanet Journal of Rare Diseases, 12(1), 99. DOI:10.1186/s13023-017-0630-4
Rasmussen, A., Radfar, L., Lewis, D., Grundahl, K., Stone, D. U., Kaufman, C. E., Rhodus, N. L., Segal, B., Wallace, D. J., Weisman, M. H., Venuturupalli, S., Kurien, B. T., Lessard, C. J., Sivils, K. L., & Scofield, R. H. (2016). Previous diagnosis of Sjögren’s Syndrome as rheumatoid arthritis or systemic lupus erythematosus. Rheumatology, 55(7), 1195–1201. DOI:10.1093/rheumatology/kew023
Aletaha, D., & Smolen, J. S. (2018). Diagnosis and Management of Rheumatoid Arthritis. Jama, 320(13), 1360. https://doi.org/10.1001/jama.2018.13103
Darrah, E., & Andrade, F. (2018). Rheumatoid arthritis and citrullination. Current Opinion in Rheumatology, 30(1), 72–78. https://doi.org/10.1097/BOR.0000000000000452
Firestein, G. S. (2003). Evolving concepts of rheumatoid arthritis. Nature, 423(6937), 356–361. https://doi.org/10.1038/nature01661
McInnes, I. B., & Schett, G. (2007). Cytokines in the pathogenesis of rheumatoid arthritis. Nature Reviews Immunology, 7(6), 429–442. https://doi.org/10.1038/nri2094
Myasoedova, E., Davis, J., Matteson, E. L., & Crowson, C. S. (2020). Is the epidemiology of rheumatoid arthritis changing? Results from a population-based incidence study, 1985–2014. Annals of the Rheumatic Diseases, 79(4), 440–444. https://doi.org/10.1136/annrheumdis-2019-216694
Safiri, S., Kolahi, A. A., Hoy, D., Smith, E., et. al. (2019). Global, regional and national burden of rheumatoid arthritis 1990–2017: A systematic analysis of the Global Burden of Disease study 2017. Annals of the Rheumatic Diseases, 78(11), 1463–1471. https://doi.org/10.1136/annrheumdis-2019-215920
Smolen, J. S., Aletaha, D., & McInnes, I. B. (2016). Rheumatoid arthritis. The Lancet, 388(10055), 2023–2038. https://doi.org/10.1016/S0140-6736(16)30173-8
Schneider, M., & Krüger, K. (2013). Rheumatoid arthritis-early diagnosis and disease
management. Deutsches Aerzteblatt Online, 110(27-28), 477–484. https://doi.org/10.3238/arztebl.2013.0477
Van der Woude, D., & van der Helm-van Mil, A. H. M. (2018). Update on the epidemiology, risk
factors, and disease outcomes of rheumatoid arthritis. Best Practice & Research Clinical Rheumatology, 32(2), 174–187. https://doi.org/10.1016/j.berh.2018.10.005