18th January 2024

Diagnosis

RA should be suspected in any adult presenting with inflammatory polyarthritis. When taking a history in someone with such a presentation, an enquiry should be made into the presence and location of joint pain, swelling and early morning stiffness. Stiffness associated with inflammatory arthritis tends to be peripheral rather than in the lower back and lasts at least 30 minutes. The duration of symptoms is also important- if symptoms have only been present for a short time (less than 6 weeks), symptoms may be more likely due to an acute viral polyarthritis than RA. Symptoms suggestive of an alternate diagnosis, e.g. psoriasis, inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), should be excluded.

A thorough physical examination to assess for synovitis, including the presence and distribution of swollen and tender joints and limited joint motion (and extra-articular manifestations), should be completed. Whilst symmetric polyarthritis (especially of the MCPs, MTPs and PIP joints) is suggestive of RA,  involvement of the DIPs is usually associated with osteoarthritis or psoriatic arthritis.

Investigations

Blood tests

Blood tests are not only useful for making the initial diagnosis of RA but are also used as baseline tests for monitoring disease activity and adverse effects of medications.

• FBC (with differential and platelet count), LFTs, U&Es, serum uric acid
• ESR and CRP are both elevated in RA- useful in initial diagnosis and for monitoring disease activity
• Immunology
  • Rheumatoid Factor (RF)- present in 70-80% of patients with RA but poor specificity (also found in healthy individuals, patients with SLE, Sjogren’s syndrome,  and those with mixed cryoglobulinemia, as well as in many other inflammatory conditions).
  • Anti-CCP – similar sensitivity as RF but much higher specificity (95-98%)
  • ANA- a negative ANA is useful in excluding SLE. It may be positive in up to ⅓ of patients with RA. If positive, anti-dsDNA and anti-Smith testing should be performed as these are highly specific for SLE.
  • Seronegative RA can be diagnosed in patients lacking both RF and anti-CCP if they have findings otherwise characteristic of RA if appropriate exclusions have been met.
• Infectious screen – especially in patients with a very short history and those who are seronegative for RF and anti-CCP:
  • Parvovirus B19
  • HBV and HCV
  • Borrelia in areas endemic for Lyme disease
  • Chikungunya virus in areas where mosquito bite-transmitted viral diseases are prevalent

Imaging

Plain radiography is usually the first mode of imaging performed in patients suspected of RA, albeit not sensitive enough to pick up changes such as bony erosions in early disease. Typical radiological findings associated with RA include osteopenia, joint space narrowing, erosions and subluxation.

Ultrasound (US) may be more useful in allowing earlier diagnosis of RA, particularly in patients with seronegative disease. It can assess soft tissues and identify synovial thickening, presence of fluid in joints and abnormalities in tendons, ligaments and entheses. Doppler US assesses for soft tissue hyperaemia and is, therefore, useful for distinguishing between active and inactive inflammatory tissues.

Magnetic resonance imaging (MRI) is more sensitive still and can evaluate all structures (including soft tissue, cartilage, and bones) which can be affected by RA.

Image Source: Wikimedia Commons (2009). Rheumatoid arthritis with unaffected carpal bones 2009, Licensed under a creative commons licence. Available for free at https://en.wikipedia.org/wiki/Rheumatoid_arthritis#/media/File:Rheumatoid_arthritis_with_unaffected_carpal_bones_2009.jpg  (Accessed: 24 November 2021).

Image Source: Wikimedia Commons (2017) Rheumatoid arthritis with carpal ankylosis 2017, Licensed under a creative commons licence. Available for free at https://en.wikipedia.org/wiki/Rheumatoid_arthritis#/media/File:Rheumatoid_arthritis_with_carpal_ankylosis_2017.jpg (Accessed 24 November 2021)

Image Source: Wikimedia Commons (2006). X-ray of right fourth PIP joint with bone erosions by rheumatoid arthritis, Licensed under a creative commons licence. Available for free at: https://upload.wikimedia.org/wikipedia/commons/6/6c/X-ray_of_right_fourth_PIP_joint_with_bone_erosions_by_rheumatoid_arthritis.jpg (Accessed: 24 November 2021).

Synovial fluid analysis

• For diagnosis or exclusion of gout, pseudogout, or an infectious arthritis if there is a joint effusion
• Analysis should include:
  • Cell count and differential
  • Crystal search
  • Gram stain and culture

Classification criteria in RA

2010 American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) Classification Criteria

The following criteria are required to be met in order to be classified as having a definite RA diagnosis:

• Presence of synovitis in at least 1 joint
• Absence of an alternative diagnosis which better explains the synovitis
• Total score of at least 6 (out of a maximum of 10) from the individual scores in the 4 domains, which include:
  • Number and site of joints involved- greater number of points for smaller joints affected.
  • Serological abnormality (RF or anti-CCP positive)
  • Elevated CRP or ESR
  • Symptom duration at least 6 weeks

Disease Activity Score (DAS)

The DAS is used to clinically measure disease activity in patients with RA and is particularly useful for targeting and objectively measuring response to treatment. It objectively measures tenderness and swelling of the shoulder, elbow, wrist, knee, MTP and PIP joints and includes a subjective measure of the patient’s general health based on a visual analogue scale.

The DAS 28 score considers the following four variables:

• The number of swollen joints (0-28)
• The number of tender joints (0-28)
• ESR or CRP
• Visual analogue scale (VAS)disease activity (0-100mm)

The formula used to calculate the score is: (0.56*√ (tender joints) +0.28*√ (swollen joints) +0.70*Ln(ESR/CRP) +0.014*VAS)

An overall score is calculated out of 10, with a score > 5.1 indicating high disease activity and a score of <3.2 indicating low disease activity. NICE recommends using the DAS as one of the criteria for starting biological therapy.

References 

• UpToDate [Internet]. Uptodate.com. 2021 [cited 10 November 2021]. Available from: https://www.uptodate.com/contents/diagnosis-and-differential-diagnosis-of-rheumatoid-arthritis/print#!#:~:text=Symmetric%20polyarthritis%2C%20particularly%20of%20the%20MCP%2C%20MTP%2C%20and%2For,suggests%20a%20diagnosis%20of%20osteoarthritis%20or%20psoriatic%20arthritis.
• Kgoebane K, Ally M, Duim-Beytell M, Suleman F. The role of imaging in rheumatoid arthritis. SA Journal of Radiology [Internet]. 2018 [cited 10 November 2021];22(1):1316. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6837821/
• Mooney J, McGee M. Early recognition of rheumatoid arthritis. Nursing and Residential Care. 2012;14(7):344-347.