Rheumatoid Arthritis (RA) Differential Diagnoses

Updated: Sep 05, 2023
  • Author: Sriya K M Ranatunga, MD, MPH, FACP, FACR; Chief Editor: Herbert S Diamond, MD  more...
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Diagnostic Considerations

Differentiation of rheumatoid arthritis (RA) from other diseases of connective tissue can be difficult; however, certain clinical features are helpful.

Rheumatic fever is characterized by the migratory nature of the arthritis, an elevated anti-streptolysin O titer, and a more dramatic and prompt response to aspirin. Carditis and erythema marginatus may occur in adults, but chorea and subcutaneous nodules virtually never do.

Systemic lupus erythematosus (SLE) is suggested by the presence of the following:

  • Butterfly rash
  • Discoid lupus erythematosus
  • Photosensitivity
  • Alopecia
  • High anti-DNA titer
  • Renal disease
  • Central nervous system (CNS) abnormalities

Degenerative joint disease (DJD) is not associated with constitutional manifestations; in contrast to the morning stiffness of RA, the joint pain from DJD is characteristically relieved by rest. Signs of articular inflammation prominent in RA are usually minimal in DJD, and in contrast to RA, osteoarthritis spares the wrist and the MCP joints.

During the early years of disease, gouty arthritis is almost always intermittent and monoarticular; in later years, it can become a chronic polyarticular process that mimics RA. Gouty tophi can at times resemble rheumatoid nodules. The early history of intermittent monoarthritis and the presence of synovial urate crystals are distinctive features of gout.

Septic arthritis can be distinguished by chills and fever, demonstration of the causative organism in joint fluid, and the frequent presence of a primary focus elsewhere (eg, gonococcal arthritis). Chronic Lyme disease typically involves only 1 joint, most commonly the knee, and is associated with positive serologic tests. Human parvovirus B19 infection in adults can occasionally mimic RA.

Polymyalgia rheumatica, which is relatively common in persons older than 50 years, occasionally causes polyarthritis. However, these patients have chiefly proximal muscle pain and stiffness and remain negative for rheumatoid factor (RF).

A variety of cancers produce paraneoplastic syndromes, including polyarthritis. One form is hypertrophic pulmonary osteoarthropathy, which is most often produced by lung and gastrointestinal carcinomas. Hypertrophic pulmonary osteoarthropathy is characterized by a rheumatoidlike arthritis associated with clubbing, periosteal new bone formation, and a negative RF test. Diffuse swelling of the hands with palmar fasciitis has also been reported with a variety of cancers, especially ovarian carcinoma.

Differential Diagnoses