Robert Terkeltaub, MD


December 30, 2002


I have a patient with recurrent attacks of acute arthritis of the knee that last for about 1 week and then subside spontaneously. Joint aspiration shows inflammatory change with no crystal but a very high synovial uric acid level (16 mg/dL; normal range is < 8 mg/dL). How would you interpret the synovial uric acid level? Is this a gouty attack?

Response from Robert Terkeltaub, MD

With respect to your first question, there is no evidence that synovial fluid uric acid correlates with serum uric acid[1] or has clinical utility for diagnosis. The second question addresses the differential diagnosis of recurrent, self-limited bouts of monoarticular inflammatory arthritis. Here, I would refer you to a classic monograph on acute monoarticular arthritis that assists clinicians in formulating a thorough differential diagnosis.[2]

Could this be a gouty attack, you ask? Clearly, the crystal-associated arthritides gout and pseudogout are prime, general considerations for the type of knee arthritis you describe in your patient. It is noteworthy that the initial synovial fluid analysis for crystals may be negative in a fraction of patients with acute gout and pseudogout, even when the fluids are collected appropriately (in the absence of EDTA that can dissolve CPPD [calcium pyrophosphate dihydrate] crystals) and analyzed appropriately by expert observers. Thus, repeat synovial fluid crystal analysis by standard compensated polarized light microscopy is indicated for recurrent, undiagnosed attacks of synovitis of this nature. If clinical suspicion warrants, the fluid also could be sent for specialized evaluation for hydroxyapatite crystals, which are non-birefringent.

In the case you cite, some of the clinical facts I would want to know include whether there is sustained hyperuricemia and what is the extent of the synovial fluid leukocytosis (and the cell differential) in these attacks. I would also want to know whether there is evidence of degenerative joint disease clinically or radiographically, and whether chondrocalcinosis (or alternatively periarticular demineralization and joint erosion) was discovered on plain films. I would also want to know if the fluids were sent for thorough microbial culture analyses.

What if there is no evidence for either crystal arthritis or infection in this knee after thorough work-up? Clinicians should keep in mind that the differential diagnosis of monoarticular attacks of knee inflammatory arthritis can broaden substantially, depending on factors such as the sex, age, concurrent medical conditions, ethnicity, and geographic location of the case, which were not stipulated here. Hence, inflammatory flares of osteoarthritis, Lyme disease, arthritis associated with inflammatory bowel disease, reactive arthritis, familial Mediterranean fever, sarcoidosis, and Behçet's disease are among the conditions that factor into the differential under differing circumstances. In addition, granulomatous infection of the knee joint such as mycobacterial disease or coccidioidomycosis can present with intermittent flares of "acute on chronic" synovitis, and a long delay in diagnosis is typical because of low clinical suspicion as well as substantial proportions of patients with negative joint fluid cultures.


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