18th January 2024

Differential diagnoses

Background

When assessing patients in early disease, the ‘typical’ features associated with RA, such as joint erosions and rheumatoid nodules, are not usually present. So, joint manifestations are often difficult to distinguish from other inflammatory polyarthritis.

Septic arthritis should be excluded in any joint that is red, hot, and swollen. This should be done via means of joint aspiration as long as there is no skin infection around the site of aspiration, and there is no metalwork inside the joint (in this case, a Trauma and Orthopaedic opinion should be sought). Septic arthritis needs to be treated with antibiotics as soon as possible.

If there are episodes of joint inflammation sequentially affecting one to several joints for hours to days (with symptom-free periods lasting days to months), consider palindromic rheumatism. Some patients do, however, go on to develop a well-defined rheumatic disease, most commonly RA or SLE. Patients with anti-CCP are more likely to develop RA.

Osteoarthritis (OA)

Despite being easily distinguishable from RA in medical textbooks, OA can cause a diagnostic conundrum in middle-aged or elderly patients when small joints of the hands are involved.

In OA, DIP joints are involved with Heberden’s nodes in this area (whereas DIP joints are spared in RA). Carpometacarpal joint of the thumb is also involved. There may be joint swelling in OA as well as in RA, but the joint swelling in OA is hard and bony, as opposed to soft, warm, boggy and tender in RA.

• Stiffness is usually absent, but if present, it is worse in the evening after exercise. If present in the morning, it lasts no more than a few minutes.
• X-rays show narrowing of joint space due to cartilage loss and osteophytes due to bone remodelling, but not erosions  (Remember LOSS in OA  (Loss of joint space, Osteophytes, Subchondral sclerosis, Subchondral cysts) vs LESS in RA (Loss of joint space, Erosions, Soft tissue swelling, Soft bones (osteopenia)

Psoriatic arthritis 

Psoriatic arthritis can be still more difficult to distinguish from RA because asymmetric polyarthritis is seen. Therefore, this diagnosis is generally made in patients who also have psoriasis and are seronegative for RF and anti-CCP. The diagnosis is made more challenging by the fact that the joint symptoms of psoriatic arthritis may precede the onset of skin disease by many years. Indeed, in some patients with a symmetric inflammatory polyarthritis, the only clue to the diagnosis of psoriatic arthritis may be a family history of psoriasis.

Although there is a clear diagnostic challenge here, the initial management of both disorders is very similar, so treatment can be initiated before necessarily distinguishing between Psoriatic arthritis and RA.

Reactive arthritis 

Reactive arthritis often presents as a monoarthritis or oligoarthritis of the large joints. RA may occasionally present similarly, particularly in the knee, where the physical signs can be identical. There are, however, some findings that are more suggestive of reactive arthritis than RA. These include :

• History of recent urethritis or enteric infection
• Asymmetric pattern of joint involvement, particularly in the hands
• Involvement of not only the joint but also the tenosynovium, entheses, and surrounding tissues. This can manifest as the characteristic “sausage” swelling in the digits of the hands and feet.
• Keratoderma blennorrhagica or circinate balanitis
• Radiological evidence of sacroiliitis and/or spondylitis
• Presence of HLA B27

Other systemic rheumatic diseases 

These disorders include Sjogren’s syndrome, dermatomyositis, and mixed connective tissue disease. They are characterised by presence of other systemic features (e.g. rashes, dry mouth and dry eyes, myositis, or nephritis) and autoantibodies not usually seen in RA.

In SLE, Jaccoud’s arthropathy (the joint deformities are not caused by joint destruction but by loosening and lengthening of periarticular structures and tendons may be confused with the characteristic joint deformities seen in RA. However, they can be differentiated by physical examination as the deformities are passively ‘correctable’ and on radiology as X-rays show no bony erosions. In addition, ESR and CRP are less well-correlated in other diseases than in RA. Whilst both are raised in RA, CRP is often normal or only minimally elevated in patients with active SLE, even when ESR is elevated.

Image Source: Wikimedia Commons (2021). Jaccoud arthropathy hand x-ray front, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Jaccoud_arthropathy_hand_x-ray_front.jpg (Accessed: 24 November 2021).

Infectious arthritis 

If the syndrome of polyarthritis is short-lived, lasting only from a few days to several weeks (rarely longer than 6 weeks), viral polyarthritis must be considered. Examples of organisms causing viral polyarthritis include Rubella, Parvovirus B19, hepatitis B and C (more commonly associated with arthralgias rather than polyarthritis) and Chikungunya.

Another example of an infectious arthritis is that of Lyme arthritis – a late manifestation of Lyme disease. This is characterised by intermittent or persistent inflammatory arthritis in a few large joints, most typically monoarthritis of the knee.

Miscellaneous diseases 

• Enteric arthritis – Usually a large-joint oligoarthritis or spondyloarthritis with sacroiliitis. However, confusion with RA can occur in patients with peripheral polyarthritis and involvement of the MCP joints.
• Crystal arthropathy (gout or pseudogout)- Can become chronic and have a polyarticular distribution, resembling RA.
• Sarcoid arthropathy- May be oligo- or polyarticular, most often affecting the ankles, knees, hands, wrists, MCP and PIP joints.

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.
• Cruz Whitley J, Aronowitz P. Jaccoud’s Arthropathy. Journal of General Internal Medicine. 2018;33(9):1583-1583.