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Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation in the synovial membrane. Its more well-known symptoms are stiffness and swelling that can last for weeks, only to disappear and then return. These symptoms can happen in five or more joints. What some may not realize is that non-specific symptoms like fatigue, malaise, or depression can precede the characteristic symptoms by weeks or months, meaning patients may be unwell for quite some time.1-3

In later stages of the disease, joint deformity and progressive physical disability are common, but by then, the damage is irreversible.4 The goal, then, is to diagnose patients earlier so that better outcomes can be achieved. Early detection can potentially save patients from irreversible joint damage, systemic complications, and considerable morbidity–all of which they may face if their disease goes undiagnosed and untreated.1

Testing using a combination of serological assays and methods could play a significant role in the early diagnosis and treatment of RA, especially if the patient's clinical presentation is ambiguous.5 When the test result is positive, the positive predictive value (PPV) represents how likely it is that a patient has the disease given that the test result is positive.6 The PPV for RA approaches 100% when a patient exhibits positivity for a combination of markers Rheumatoid Factor (RF IgM), RF IgA, and a second-generation anti-Cyclic Citrullinated Peptide (CCP) IgG test.5 Testing for both anti-CCP and RF is beneficial when excluding the diagnosis of RA, rather than testing for either antibody alone.7

Rheumatoid arthritis: The most prevalent autoimmune disease1,4

Test Results Help Aid in the Diagnosis

One of the most important and helpful tools in reaching a RA diagnosis is serological testing. Test results from one test alone give limited help in reaching a diagnosis. There are multiple blood tests that can be performed in the diagnostic process.

International guidelines classification criteria recommend laboratory testing for:9

  • Rheumatoid Factor (RF IgM)
  • Anti-Cyclic Citrullinated Peptide (CCP)
  • Erythrocyte Sedimentation Rate (ESR)
  • C-Reactive Protein (CRP)

Numerous international guidelines recommend RF IgM-RF and anti-CCP as first-line tests

CCP antibodies appear in the early stages of rheumatoid disease, and RF of all isotypes (IgM and IgA) predate the onset of RA by several years.8 The detection of these isotypes, particularly IgA and IgM, have been found to be significant predictors of RA.9

If patients are exhibiting one or more common RA symptoms, test results can help provide a quicker diagnosis while ruling out other possible diseases. Research has shown definitive serological overlap between RA and systemic lupus erythematosus (SLE), known in combination as “rhupus,” Hashimoto’s disease, systemic sclerosis, and various connective tissue diseases (CTDs).10-13


Early identification and management of RA can also:14,15

  • Positively affect the course of the disease
  • Prevent the development of potentially debilitating joint erosion
  • Ameliorate progression of erosive and overlapping diseases


Food allergen

Personalized management plans and ongoing testing can help maintain treatment progress

Though RA is chronic and incurable, effective management can help reduce symptom flares and improve overall quality of life. Remission may even be possible if the disease is diagnosed and treated early.23


Clinicians also use the following well-established clinical guidelines to aid in the creation of individualized treatment strategies for patients with RA:


  1. Suresh E. Diagnosis of early rheumatoid arthritis: what the non-specialist needs to know. J R Soc Med. 2004;97:421-424.
  2. Louati K, Berenbaum F. Fatigue in chronic inflammation- a link to pain pathways. Arthritis Res Ther. 2015;17:254.
  3. Arthritis Foundation. Palindromic Rheumatism. http://www.arthritis.org/about-arthritis/types/palindromic-rheumatism/. Accessed October 2017.
  4. Symmons D, Mathers C, Plefler B. The global burden of rheumatoid arthritis in the year 2000. Global Burden of Disease 2000. http://www.who.int/healthinfo/statistics/bod_rheumatoidarthritis.pdf. Accessed December 2017.
  5. Jaskowski TD, Hill HR, Russo KL, et al. Relationship between rheumatoid factor isotypes and IgG anti-cyclic citrullinated peptide antibodies. J Rheumatol. 2010;37:1582-1588.
  6. Ghaaliq Lalkhen A, McCluskey A. Clinical tests: sensitivity and specificity. Continuing Education in Anaesthesia Critical Care & Pain. 2008;8221-8223.
  7. Castro C, Gourley M. Diagnostic testing and interpretation of tests for autoimmunity. J Allergy Clin Immunol. 2010;125(2 Suppl 2):S238-S247.
  8. 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 Sep;62(9):2569-81.
  9. Jónsson T1, Steinsson K, Jónsson H Combined elevation of IgM and IgA rheumatoid factor has high diagnostic specificity for rheumatoid arthritis. Rheumatol Int. 1998;18(3):119-22.
  10. Dougados M, Soubrier M, Antunez A, et al. Prevalence of comorbidities in rheumatoid arthritis and evaluation of their monitoring: results of an international, cross-sectional study (COMORA). Ann Rheum Dis. 2014;73(1):62-68.
  11. Icen M, Nicola PJ, Maradit-Kremers H, et al. Systemic Lupus Erythematosus Features in Rheumatoid Arthritis and Their Impact on Overall Mortality. J Rheumatol. 2009;36(1):50-57.
  12. Robazzi TC, Adan LF. Autoimmune thyroid disease in patients with rheumatic diseases. Rev Bras Reumatol. 2012;52(3):417-430.
  13. Szücs G, Szekanecz Z, Zilahi E, et al. Systemic sclerosis-rheumatoid arthritis overlap syndrome: a unique combination of features suggests a distinct genetic, serological and clinical entity. Rheumatology. 2007;46(6):989-993
  14. Raza K, Buckley CE, Salmon M, et al. Treating very early rheumatoid arthritis. Best Pract Res Clin Rheumatol. 2006(5):849-863.
  15. Demoruelle MK, Deane KD. Treatment strategies in early rheumatoid arthritis and prevention of rheumatoid arthritis. Curr Rheumatol Rep. 2012;14(5):472-480.