Undifferentiated Inflammatory Arthritis

Inflammatory arthritis is a term used to describe any condition in which there is inflammation of the joint space or synovium (i.e., synovitis). In most cases, this is due to autoimmune disease, the presence of crystals, autoinflammatory disease, or infection. The differential diagnosis for inflammatory arthritis is quite broad; however, because differentiating between the various causes of inflammatory arthritis often involves assessment of chronicity and evaluation for associated symptoms or diseases that may not be readily apparent upon initial presentation, some patients with early inflammatory arthritis (within the first year of presentation) may be considered to have “undifferentiated” inflammatory arthritis until a clearer diagnosis can be made.

Evaluation

History and physical examination: Careful history taking and a thorough physical examination will aid in the identification of extra-articular manifestations, the distribution and nature of the arthritis, and the time course of the disease process. Important aspects of history and examination include:

• number of joints involved: monoarticular (one), oligoarticular (two to four), or polyarticular (more than four)

• distribution and timing of joints involved

  • symmetric or asymmetric

  • peripheral (distal to hips and shoulders) or axial (proximal to hips and shoulders)

  • acute/subacute (<6 weeks) or chronic (>6 weeks)

  • episodic (periods of synovitis separated by asymptomatic periods), migratory (quickly migrating from one joint to the next without periods of absent synovitis), or persistent (settling in joints that remain affected for prolonged periods of time)

  • favoring or sparing certain joints

• mucocutaneous abnormalities (e.g., oral ulcers, nail pitting, psoriasis, sclerodactyly, photosensitive rash, alopecia) and their distribution

• Raynaud phenomenon

• tendon involvement (e.g., tenosynovitis, tendinitis)

• lymphadenopathy and organomegaly

• ocular inflammation (e.g., uveitis, scleritis, keratitis, retinal vasculitis)

• pulmonary abnormalities (e.g., interstitial lung disease, lung nodules)

• muscle weakness of limbs, head, neck, and pharynx

• abdominal symptoms (such as hematochezia, diarrhea, and abdominal pain)

• recent travel, joint injury, or infections (including sexually transmitted infections)

Investigations: The history and physical examination will direct sensible additional investigation to include or exclude the provisional diagnoses. Not all tests are required for all patients. The following table lists some relevant investigations.

Synovial fluid analysis: In certain situations, such as when septic arthritis is suspected, synovial fluid analysis is vital. Although the table below is a good guide, there is significant overlap in the synovial fluid white blood cell (WBC) count for several conditions; for example, septic arthritis could be present with <50,000 cells/mm³ and a noninflammatory condition (such as osteoarthritis) could exist with a synovial fluid count >2000 cells/mm³ (though rarely much more). In general, the higher the synovial fluid WBC count, the greater the concern for septic arthritis. Malignancies rarely affect the joint; as a result, synovial fluid cytology is a relatively low-yield test and should not be tested routinely.

Treatment

• It is tempting to treat undifferentiated inflammatory arthritis with glucocorticoids to reduce suffering; however, the underlying pathological process will likely be altered. It is preferable to defer the use of glucocorticoids until the investigation for the underlying cause has been completed and infection has been ruled out.

• Nonsteroidal anti-inflammatory drugs (NSAIDs), both oral and topical, often provide a degree of symptomatic relief during the diagnostic evaluation.

• Once infection has been ruled out, patients with a moderate-to-high severity of symptomatology and associated functional limitation are typically treated with glucocorticoid tapers.

• If the inflammatory arthritis is chronic (>6 weeks) or relapses with glucocorticoid tapers, or if the evaluation is suggestive of a known chronic inflammatory arthritis (e.g., rheumatoid arthritis, axial psoriatic arthritis, axial spondyloarthritis), disease-modifying antirheumatic drugs (DMARDs) such as hydroxychloroquine, methotrexate, or biologic agents are typically initiated.

• Due to the importance of early initiation of treatment to prevent joint damage and functional impairment, patients with undifferentiated inflammatory arthritis should be referred to rheumatology for management.