How can rheumatoid arthritis (RA) affect my body and my health?

Patients with rheumatoid arthritis (RA) can expect to have joint swelling associated with synovial proliferation, which typically presents as a symmetric polyarthritis.¹ Patients with RA may experience pain, stiffness, swelling, deformity, and loss of function if untreated. RA also can include extra-articular manifestations, including coronary artery disease, rheumatoid nodules, interstitial lung disease, vasculitis, and other systemic comorbid conditions.² The development of these manifestations from RA can occur over time and with an increase in RA disease duration. The 2015 American College of Rheumatology (ACR) Guideline defines early RA as, “RA with duration of disease/symptoms of <6 months, where ‘duration’ denotes the length of time the patient has had symptoms/disease, not the length of time since RA diagnosis” and established RA is defined as, “RA with duration of disease/symptoms of >6 months or meeting 1987 ACR RA classification criteria.”³ Since the introduction of biologic disease modifying anti-rheumatic drugs (DMARDs), the safety and efficacy of these medications have been evaluated,⁴ and the ACR has endorsed the treat-to-target approach set by the European League Against Rheumatism.⁵ Under this approach, the target is to achieve clinical remission or low disease activity through treatment escalation for RA by either increasing the dose of DMARDs or adding another DMARD or biologic to the treatment plan. This approach was endorsed by the ACR also as a way to decrease the development of extra articular manifestations from RA.

It is important to start treatment for RA early, as delayed treatment can be associated with deformities and worse outcomes, such as disability.^4-9 In a study of 183 patients with untreated RA at baseline, 46 (25%) patients developed deformities after one year and 62 (34%) patients within two years, and those with deformities had higher disease activity during the first 5 years of the disease.⁷ This highlights the importance of aggressive and early treatment. One of the main outcomes measured in clinical trials is radiographic progression, defined as joint space narrowing, loss of joint alignment, and/or development of bone erosions.¹⁰ This is important because these initial changes are those that can precede joint deformities. A systematic review of 63 studies that included 34 randomized controlled trials showed that biologic DMARDs used in combination with methotrexate produce better radiographic outcomes than biologic DMARDs or methotrexate alone.¹¹

Patients in consistent remission had lower pain scores, fatigue scores, and had less disability compared to patients who were not in remission or in low disease activity.^8,12 In addition, a longitudinal study of 2045 patients showed no differences in Health Assessment Questionnaire (self-reported functional status) progression or incident orthopedic operations between patients in remission and with low disease activity.⁹ However, there was a significantly higher incidence of major surgery in patients with high (odds ratio [OR] 2.48, 95% confidence interval [CI] [1.5 – 4.11]), high-moderate (OR 2.16, 95% CI [1.32 – 3.52]) and low-moderate (OR 2.07, 95% CI [1.28 – 3.33]) disease activity scores compared to patients in remission. Still, it may be possible for patients in remission to experience further damage.¹³

While joints, particularly the hands, wrists, shoulders, hips, knees and ankles, are most commonly affected, the prevalence of extra-articular RA is about 40%.^14,15 Cardiac disease is an important long-term outcome of RA. In autopsy studies, pericarditis has been shown to be present in 50% of patients with RA.¹⁶ The risk of cardiovascular events in women with RA such as a myocardial infarction is also increased compared to women without RA (adjusted relative risk 2.0, 95% CI [1.23 – 3.29], p=0.005).¹⁷ The incidence of heart failure is significantly higher among patients with RA compared to patients without RA (1.99 versus 1.16 cases per 100 person-years).¹⁸ Pleural disease is usually asymptomatic, with only 10% of cases detected clinically.¹⁹ However, it is present in up to 50% of patients with RA in autopsy studies.¹⁹ Interstitial lung disease develops in 9.4% of patients with RA, and usually presents as asymmetric bilateral basilar interstitial abnormalities on radiographs.^19,20 Rheumatoid nodules occur in about 20% of patients with RA, mainly in those who are rheumatoid factor-positive.¹⁹ They can develop in the elbows, finger joints, ischial and sacral prominences, occipital scalp, and Achilles tendon. Many patients with RA also develop osteopenia and osteoporosis²¹ and have a 1.5 to 2-fold higher prevalence of osteoporosis than the general population, which can also be exacerbated by the use of glucocorticoids in treating RA for some individuals.²² Anemia is common, with a prevalence ranging from 33 – 60%, and correlates with disease activity and articular inflammation.¹⁹ RA also may involve the eyes with keratoconjunctivitis sicca being the most common ocular manifestation occurring in at least 10-20% of patients with RA.¹⁹ Systemic vasculitis is uncommon in patients RA but often occurs in patients with severe and long-standing rheumatoid disease of more than 10 years' duration.²³

Common Extra-articular Manifestations of RA²⁴

Cardiovascular

• Premature atherosclerosis, coronary and peripheral vascular disease
• Pericarditis
• Valvular defects
• Arrhythmia, conduction defects
• Myocarditis
• Asymptomatic myocardial disease^25,26
• Heart failure (particularly with preserved ejection fraction)
• Vasculitis

Dermatologic

• Rheumatoid nodules
• Treatment-related rashes

Ophthalmologic

• Keratococonjuctivities sicca (secondary Sjogren syndrome)
• Episcleritis
• Scleritis

Pulmonary

• Pulmonary fibrosis
• Interstitial lung disease (nonspecific interstitial pneumonia, usual interstitial pneumonia, organizing pneumonia)
• Nodules
• Pleural effusion
• Pleuritis
• Bronchiectasis
• Cryptogenic organizing pneumonia

Musculoskeletal

• Muscle weakness (muscle atrophy due to joint inflammation, myositis, or drug-induced myopathy)^19,27
• Osteopenia²¹
• Osteoporosis^22,28

Gastrointestinal

• Xerostomia
• Gastritis or peptic ulcer disease (from nonsteroidal anti-inflammatory drugs (NSAIDs) or glucocorticoids)
• Stomatitis (from methotrexate)

Renal

• Glomerulonephritis (usually mesangioproliferative)
• Proteinuria (rarely due to secondary amyloidosis)
• Treatment-related kidney injury (from NSAIDs)

Hepatic

• Portal fibrosis
• Treatment-related hepatitis/cirrhosis

Neurologic

• Cervical spine subluxation/atlantoaxial instability
• Peripheral nerve entrapment (carpal tunnel syndrome)

Hematologic

• Anemia¹⁹
• Thrombocytosis¹⁹
• Lymphadenopathy
• Leukopenia (as part of Felty syndrome)
• Lymphoma

Risk for infections

• Due to medications used to treat RA

^{Note: While medications used to treat RA can increased the risk for infections, having uncontrolled RA by not using medications to control RA disease activity can also increase the risk of developing an infection}.

^References

1. Cush JJ, Weinblatt ME, Kavanaugh A. Rheumatoid arthritis: early diagnosis and treatment. 3rd ed. Islip, NY: Professional Communications, Inc.; 2010.
2. Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. Lancet 2016; 388 (10055): 2023-2038.
3. Singh JA, Saag KG, Bridges SL, Jr., et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken) 2016; 68 (1): 1-25.
4. Singh JA, Christensen R, Wells GA, et al. Biologics for rheumatoid arthritis: an overview of Cochrane reviews. Cochrane Database of Systematic Reviews 2009; (4).
5. Smolen JS, Breedveld FC, Burmester GR, et al. Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force. Ann Rheum Dis 2016; 75 (1): 3-15.
6. Abu-Shakra M, Toker R, Flusser D, et al. Clinical and radiographic outcomes of rheumatoid arthritis patients not treated with disease-modifying drugs. Arthritis Rheum 1998; 41 (7): 1190-1195.
7. Eberhardt K, Johnsson PM. Hand deformities are important signs of disease severity in patients with early rheumatoid arthritis. Rheumatology 2009; 48 (11): 1398-1401.
8. Navarro-Millan I, Chen L, Greenberg JD, et al. Predictors and persistence of new-onset clinical remission in rheumatoid arthritis patients. Semin Arthritis Rheum 2013; 43 (2): 137-143.
9. Nikiphorou E, Norton S, Young A, et al. Association between rheumatoid arthritis disease activity, progression of functional limitation and long-term risk of orthopaedic surgery: combined analysis of two prospective cohorts supports EULAR treat to target DAS thresholds. Ann Rheum Dis 2016; 75 (12): 2080-2086.
10. van der Heijde D, van der Helm-van Mil AH, Aletaha D, et al. EULAR definition of erosive disease in light of the 2010 ACR/EULAR rheumatoid arthritis classification criteria. Ann Rheum Dis 2013; 72 (4): 479-481.
11. Combe B, Lula S, Boone C, et al. Effects of biologic disease-modifying anti-rheumatic drugs on the radiographic progression of rheumatoid arthritis: a systematic literature review. Clin Exp Rheumatol 2018; 36: 658-667.
12. Felson DT, Smolen JS, Wells G, et al. American College of Rheumatology/European League against Rheumatism provisional definition of remission in rheumatoid arthritis for clinical trials. Ann Rheum Dis 2011; 70 (3): 404-413.
13. Molenaar ET, Voskuyl AE, Dinant HJ, et al. Progression of radiologic damage in patients with rheumatoid arthritis in clinical remission. Arthritis Rheum 2004; 50 (1): 36-42.
14. Turesson C, O'Fallon WM, Crowson CS, et al. Extra-articular disease manifestations in rheumatoid arthritis: incidence trends and risk factors over 46 years. Ann Rheum Dis 2003; 62 (8): 722-727.
15. Myasoedova E, Crowson CS, Turesson C, et al. Incidence of extraarticular rheumatoid arthritis in Olmsted County, Minnesota, in 1995-2007 versus 1985-1994: a population-based study. J Rheumatol 2011; 38 (6): 983-989.
16. Bonfiglio T, Atwater EC. Heart disease in patients with seropositive rheumatoid arthritis; a controlled autopsy study and review. Arch Intern Med 1969; 124 (6): 714-719.
17. Solomon DH, Karlson EW, Rimm EB, et al. Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis. Circulation 2003; 107 (9): 1303-1307.
18. Crowson CS, Nicola PJ, Kremers HM, et al. How much of the increased incidence of heart failure in rheumatoid arthritis is attributable to traditional cardiovascular risk factors and ischemic heart disease? Arthritis Rheum 2005; 52 (10): 3039-3044.
19. M Hochberg AS JS, M Weinblatt, M Weisman. Rheumatology. In: 5th ed. Philadelphia, PA: Elsevier Mosby; 2011:823-972.
20. Turesson C, O'Fallon WM, Crowson CS, et al. Occurrence of extraarticular disease manifestations is associated with excess mortality in a community based cohort of patients with rheumatoid arthritis. J Rheumatol 2002; 29 (1): 62-67.
21. Deal C. Bone loss in rheumatoid arthritis: systemic, periarticular, and focal. Curr Rheumatol Rep 2012; 14 (3): 231-237.
22. Hauser B, Riches PL, Wilson JF, et al. Prevalence and clinical prediction of osteoporosis in a contemporary cohort of patients with rheumatoid arthritis. Rheumatology (Oxford) 2014; 53 (10): 1759-1766.
23. M Hochberg AS JS, M Weinblatt, M Weisman. Rheumatology. In: 5th ed.2011:841-845.
24. Sparks JA. Rheumatoid Arthritis. Ann Intern Med 2019; 170 (1): ITC1-ITC16.
25. Kobayashi Y, Giles JT, Hirano M, et al. Assessment of myocardial abnormalities in rheumatoid arthritis using a comprehensive cardiac magnetic resonance approach: a pilot study. Arthritis Res Ther 2010; 12 (5): R171.
26. Ntusi NAB, Piechnik SK, Francis JM, et al. Diffuse myocardial fibrosis and inflammation in rheumatoid arthritis: insights from CMR T1 mapping. JACC Cardiovasc Imaging 2015; 8 (5): 526-536.
27. Halla JT, Koopman WJ, Fallahi S, et al. Rheumatoid myositis. Clinical and histologic features and possible pathogenesis. Arthritis Rheum 1984; 27 (7): 737-743.
28. Haugeberg G, Orstavik RE, Uhlig T, et al. Clinical decision rules in rheumatoid arthritis: do they identify patients at high risk for osteoporosis? Testing clinical criteria in a population based cohort of patients with rheumatoid arthritis recruited from the Oslo Rheumatoid Arthritis Register. Ann Rheum Dis 2002; 61 (12): 1085-1089.