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Rheumatoid Arthritis: Overview, Diagnosis, and Treatment

About Rheumatoid Arthritis

Morning stiffness, fatigue, joint pain, and swelling are common initial symptoms of rheumatoid arthritis (RA) do not differ substantially from other forms of inflammatory arthritis.1 There is also a wide range of other conditions that can mimic RA. The ambiguity and overlap of symptoms—especially in its early stages—can make RA difficult to diagnose.

Early detection can potentially save patients from the irreversible joint damage, systemic complications, and considerable morbidity—all of which they may face if their disease goes undiagnosed and untreated.1

RA is a systemic autoimmune disease characterized by chronic inflammation in the synovial membrane of the joint. In later stages of the disease, joint deformity and progressive physical disability6 are common, but by then, the damage is irreversible. The goal, though, is to diagnose patients earlier so that better outcomes can be achieved.

1% of the world's population    

Rheumatoid arthritis affects approximately 1 percent of the world’s population.1,5

Rheumatoid arthritisis (RA) is a systemic autoimmune disease characterized by chronic inflammation in the synovial membrane of the joint. Common, initial clinical features include:2-4


Stiffness: Patients may note being particularly stiff in the morning, and may also note pain on movement and tenderness.    

Palindromic joint swelling: Patients often report swelling in one or two joints that lasts a few days to weeks; it may disappear completely, only to return later in the same or other joints, with a pattern increasing over time.


Polyarticular joint involvement: Patients may report symptoms in five or more joints, though this is highly variable.

Non-specific systemic symptoms: Patients may experience primarily fatigue, malaise, or depression, and these symptoms frequently precede other symptoms by weeks to months.

A clinical history and examination are chief to identifying rheumatoid arthritis (RA), with imaging and laboratory tests providing additional specificity that can help you diagnose patients and begin treatment earlier.10,11

Rheumatoid arthritis: Refining differential diagnosis through testing

One of the most important and helpful criteria in reaching a diagnosis is the blood test to identify a specific set of antibodies that are known biomarkers for assessing rheumatoid arthritis. There isn’t one single test that can produce a diagnosis, but there are multiple blood tests that can be performed in the diagnostic process.

International guidelines classification criteria recommend laboratory testing for:6

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

Numerous international guidelines recommend RF IgM and anti-CCP as first line tests. CCP antibodies appear in the early stages of rheumatoid disease, and RF IgM is the major RF autoantibody in RA and are detected in 60 percent to 80 percent of RA patients.7,8

RF has proven to be the most useful disease marker of RA,9 and the association between high titer RF IgM status and a poor prognosis indicates that RF may have a role in the pathogenesis of RA.

As active disease approaches, RF IgM and CCP levels surpass RF IgA levels.

A clinical history and examination are chief to identifying RA, with imaging and laboratory tests providing additional specificity that can help you diagnose patients and begin treatment earlier.10,11

Many tests measure rheumatoid factor (RF) using nephelometry or turbidometry. However, using an RA panel that can distinguish between the different RF isotypes—RF IgA and RF IgM in particular—can give you important additional diagnostic guidance.12-14

Testing can help provide a quicker diagnosis, while potentially ruling out other possible diseases, and is simple, specific, and reliable.

Classification criteria

The 2010 American College of Rheumatology/European League Against Rheumatism collaborative initiative classification criteria are based on clinical presentation of synovitis (joint swelling), serology, acute-phase reactants, and duration of symptoms. Once other conditions have been ruled out, a patient is classified as having RA if a score of ≥ 6 out of a possible 10 is reached.15

Not sure which allergy or autoimmune disease could be behind your patient’s symptoms? Use this interactive tool to take the next step in making your differential diagnosis.

Testing Confidence

Testing Increases Diagnostic Confidence

Adding diagnostic testing to aid in a differential diagnosis has been shown to increase confidence in diagnosis to 90 percent.i,ii Conventionally, a diagnosis of allergic or autoimmune disease relies on the case history and a physical examination. However, adding diagnostic testing to aid in a differential diagnosis has been shown to increase confidence in diagnosis.i,ii Diagnostic testing can also help to improve the patient’s quality of life and productivity, reduce costs associated with absenteeism, and optimize use of medication, in addition to decreasing unscheduled healthcare visits.iii,iv 

i. Duran-Tauleria E, Vignati G, Guedan MJ, et al. The utility of specific immunoglobulin E measurements in primary care. Allergy. 2004;59 (Suppl78):35-41.
ii. NiggemannB, Nilsson M, Friedrichs F. Paediatric allergy diagnosis in primary care is improved by in vitro allergen specific IgE testing. Pediatr Allergy Immunol. 2008;19:325-331
iii. Welsh N, et al. The Benefits of Specific Immunoglobulin E Testing in the Primary Care Setting. J Am Pharm Assoc. 2006;46:627.
iv. Szeinbach SL, Williams B, Muntendam P, et al. Identification of allergic disease among users of antihistamines. J Manag Care Pharm. 2004; 10 (3): 234-238

Learn about autoimmune disease.

Learn more about testing.

Management and care of patients with rheumatoid arthritis

Early treatment is imperative for rheumatoid arthritis (RA), as joint destruction begins within a few weeks of symptom onset.16 Therapeutic goals include function and quality of life preservation, pain and inflammation minimization, joint protection, and complication control.16 The goals of RA management are to:17

  • Prevent or control joint damage
  • Prevent loss of function
  • Decrease the patient’s pain

Across the American College of Rheumatology guidelines, the ACR Subcommittee on Rheumatoid Arthritis recommends that patients with suspected RA be referred to a rheumatologist within three months of presentation for diagnosis and initiation of treatment with disease modifying antirheumatic drugs (DMARDs).16

Pharmacologic therapy for RA often consists of combinations of NSAIDs, DMARDs, and/or glucocorticoids.16,17

NOTE: 2019 American College of Rheumatology Guideline for the Management of Rheumatoid Arthritis (final publication of updated guideline anticipated in late 2019/early 2020) 

References
  1. Suresh E. Diagnosis of early rheumatoid arthritis: what the non-specialist needs to know. J R Soc Med. 2004;97:421-424.
  2. Revenson T, Schiaffino KM, Majerovitz D, et al. Social Support as a Double-edged Sword: The Relation of Positive and Problematic Support to Depression Among Rheumatoid Arthritis Patients. Soc Sci Med. 1991;33(7)807-813.
  3. Louati K, Berenbaum F. Fatigue in chronic inflammation- a link to pain pathways. Arthritis Res Ther. 2015;17:254.
  4. Arthritis Foundation. Palindromic Rheumatism. http://www.arthritis.org/about-arthritis/types/palindromic-rheumatism/. Accessed October 2017. 
  5. Herold M, Boeser V, Russe E, et al. Anti-CCP: History and its usefulness. Clin & Dev Immuno. 2005;12(2):131-135.
  6. Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Athritis Rheum. 2010 Sep;62(9):2569-81.
  7. Schellekens GA, Visser H, de Jong BA, et al. The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide. Arthritis Rheum. 2000;43(1):155-63.
  8. Berglin E, Padyukov L, Sundin U, et al. A combination of autoantibodies to cyclic citrullinated peptide (CCP) and HLA-DRB1 locus antigens is strongly associated with future onset of rheumatoid arthritis. Arthritis Res Ther. 2004;6(4): R303–R308.
  9. Song YW, Kang EH. Autoantibodies in rheumatoid arthritis: rheumatoid factors and anticitrullinated protein antibodies. Q J Med. 2010;103:139-146.
  10. Heidari B. Rheumatoid Arthritis: Early diagnosis and treatment outcomes. Caspian J Intern Med. 2011;2(1):161-170.
  11. Da Mota LMH, Laurindo I, dos Santos Neto L, et al. Imaging diagnosis of early rheumatoid arthritis. Rev Bras Reumatol. 2012;52(5):757-766
  12. Bobbio-Pallavicini F, Caporali R, Alpini C, et al. High IgA rheumatoid factor levels are associated with poor clinical response to tumour necrosis factor α inhibitors in rheumatoid arthritis. Ann Rheum Dis. 2007;66(3):302-307.
  13. Jónsson T, Valdimarsson H. Is measurement of rheumatoid factor isotypes clinically useful? Ann Rheum Dis. 1993;52(2):161-164.
  14. Shakiba Y, Koopah S, Jamshidi AR, et al. Anti-cyclic citrullinated peptide antibody and rheumatoid factor isotypes in Iranian patients with rheumatoid arthritis: evaluation of clinical value and association with disease activity. Iran J Allergy Asthma Immunol. 2014;13(3):147-156.
  15. 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.
  16. Rindfleisch JA, Muller D. Diagnosis and management of rheumatoid arthritis. Am Fam Physician. 2005 Sep 15;72(6):1037-47.
  17. American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the management of rheumatoid arthritis: 2002 Update. Arthritis Rheum. 2002 Feb;46(2):328