Elderly patients who complain of joint pain and stiffness usually have osteoarthritis (OA), but other forms of arthritis should also be considered. Rheumatoid arthritis (RA), for example, is an autoimmune disorder rather than a degenerative disorder that affects patients at all ages. Early diagnosis and treatment of RA can prevent or minimize irreversible joint damage.1 So it’s especially important to diagnose or rule out RA when a person presents with joint pain. In this newsletter, we’ll talk about a way to optimize diagnosis of early RA (symptoms <6 months duration).2
The American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) has created a classification scheme designed to identify early RA. Diagnosis begins with a history and physical. It’s important to note the number and size of joints involved and how long the patient has had symptoms. Inflammatory marker (C-reactive protein [CRP] and/or erythrocyte sedimentation rate [ESR]) test results, as well as rheumatoid factor (RF) and cyclic citrullinated peptide (CCP) antibody test results, should be obtained. This information is used in a scoring system designed to identify early-stage patients who are at high risk of persistent and/or erosive disease.3 Details of the scoring system and classification criteria can be found in the Figure and reference 3.
Optimizing Early RA Diagnosis
As discussed above, use of the ACR/EULAR classification criteria can help identify early RA. The serologic markers used (RF and CCP), however, are more sensitive in established RA than in early RA (Table). Combined use of RF and CCP does improve sensitivity, but it is still relatively low for early disease. Between 28% and 44% of early RA patients are seronegative, ie, they test negative for both RF and CCP.4,5 A novel biomarker, called 14-3-3η (eta), offers a way to further increase sensitivity for early disease. 14-3-3η is released from joints that are inflamed by RA. The 14-3-3η protein is slightly more sensitive than the other markers in early RA. It is more specific than RF but less specific than CCP (Table).4 When 14-3-3η is combined with RF and CCP, sensitivity for early RA diagnosis rises to nearly 80%. This improved sensitivity is due to the 14-3-3η test identifying 21% of seronegative patients with early RA.6
How the Laboratory Can Help
Quest Diagnostics offers a selection of tests for ruling in, or ruling out, RA. These include tests for the general inflammatory markers (ESR, CRP) and the serologic markers (RF, CCP, and 14-3-3η). The serologic tests can be ordered separately or in a panel. Quest also offers tests that help differentiate RA from other conditions such as primary Sjögren syndrome, systemic sclerosis, gout, OA, and certain infections. Viral infections that may present with joint pain include hepatitis B and C, parvovirus B19, and rubella. Mosquito- and tick-borne infections such as chikungunya and Lyme disease may also cause joint pain.
Prevalence estimates for arthritis in the US population are:7-9
– 30.8 million people with osteoarthritis
– 8.3 million people with gout
– 1.5 million people with rheumatoid arthritis
– 740,000 to 2.0 million people with psoriatic arthritis
You can find more information at these Web sites:
– The Quest Diagnostics Test CenterRheumatoid Arthritis
Diagnostic Panel IdentRA® with 14-3-3 eta test summary
– Osteoarthritis and Rheumatoid Arthritis clinical focus
– Autoimmune Rheumatic and Related Diseases clinical focus
ACR/EULAR classification criteria for RA: ard.bmj.com/content/69/9/1580.full
American Academy of Family Physicians guidelines for RA diagnosis and management:
1. Nell VP, Machold KP, Eberl G, et al. Benefit of very early referral and very early therapy with disease-modifying anti-rheumatic drugs in patients with early rheumatoid arthritis. Rheumatology (Oxford). 2004;43:906-914.
2. Singh JA, Saag KG, Bridges SL, Jr., et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol. 2016;68:1-26.
3. Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62:2569-2581.
4. Maksymowych WP, Naides SJ, Bykerk V, et al. Serum 14-3-3 eta is a novel marker that complements current serological measurements to enhance detection of patients with rheumatoid arthritis. J Rheumatol. 2014;41:2104-2113.
5. Jansen AL, van der Horst-Bruinsma I, van Schaardenburg D, et al. Rheumatoid factor and antibodies to cyclic citrullinated Peptide differentiate rheumatoid arthritis from undifferentiated polyarthritis in patients with early arthritis. J Rheumatol. 2002;29:2074-2076.
6. Naides SJ, Marotta A. 14-3-3eta in “Seronegative” Rheumatoid Arthritis. J Rheumatol. 2015;42:1995.
7. Arthritis-related statistics. Centers for Disease Control and Prevention website. www.cdc.gov/arthritis/data_statistics/arthritis-related-stats.htm. Updated April 12, 2016. Accessed April 18, 2016.
8. Gelfand JM, Gladman DD, Mease PJ, et al. Epidemiology of psoriatic arthritis in the population of the United States. J Am Acad Dermatol. 2005;53:573.
9. Helmick CG, Lee-Han H, Hirsch SC, et al. Prevalence of psoriasis among adults in the U.S.: 2003-2006 and 2009-2010 National Health and Nutrition Examination Surveys. Am J Prev Med. 2014;47:37-45.