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Previous Volume 355:421-422 July 27, 2006 Number 4 Next

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To the Editor: The medical mystery in the June 1 issue¹ involved a 51-year-old woman with a 15-year history of rheumatoid arthritis, who presented with swelling and a loss of function of the right shoulder. Microscopy of the synovial fluid drawn from this shoulder showed geometric plates with notched corners, pathognomonic of monohydrate cholesterol crystals (Figure 1A). Analysis of the synovial fluid revealed a leukocyte count of 2100 per cubic millimeter, a total cholesterol level of 7.8 g per liter, a low-density lipoprotein cholesterol level of 6.1 g per liter, a high-density lipoprotein cholesterol level of 1.7 g per liter, and a triglyceride level of 0.83 g per liter. The plasma lipid profile was normal.

View larger version (52K): [in this window] [in a new window]   Figure 1. Cholesterol Crystals in Synovial Fluid. In Panel A, monohydrate cholesterol crystals are identified on the basis of their geometric plates with notched corners. Panel B clearly shows the milky appearance of the patient's synovial fluid.

 
Cholesterol crystals are found only sporadically in the synovial fluid of patients with rheumatoid arthritis. Such crystals may appear in two morphologic forms: large, flat, rectangular plates that are negatively birefringent (doubly refracting) with notched corners, ranging from 8 to 100 µm long and consisting of monohydrate cholesterol, or rod-shaped, helical birefringent crystals, ranging from 2 to 20 µm long and consisting of anhydrate cholesterol. Since these large cholesterol plates are difficult to clear, they are thought to play a role in the perpetuation of the arthritis.

Tim L. Jansen, M.D., Ph.D.
Anneke Spoorenberg, M.D., Ph.D.
Medisch Centrum Leeuwarden
8934 AD Leeuwarden, the Netherlands

Editor's note: We received 658 responses to this medical mystery from 59 countries. Fifty-nine percent of the responses were from physicians in practice, 21 percent from physicians in training, 13 percent from medical students, and 7 percent from other readers. As with past medical mysteries, many of the responses reflected a team effort — such as members of a training program submitting a group response after discussing the case in a teaching conference.

Twenty-seven percent of the respondents correctly identified cholesterol crystals in the synovial fluid. Forty-nine percent suggested the presence of other crystalline diseases, including gout (urate crystals) and pseudogout (calcium pyrophosphate crystals). Nine percent suggested an infectious arthritis, such as that due to Mycobacterium tuberculosis, as the cause. The remaining 15 percent of respondents suggested a variety of conditions, including amyloidosis, multiple myeloma, sarcoidosis, gold deposition from intraarticular injections, and a malignant effusion, to explain the findings.

Important clues to the correct diagnosis include the finding of variably birefringent, platelike crystals with notched corners under polarizing microscopy (Figure 1A) and milky synovial fluid on gross analysis (Figure 1B).

References

1. Jansen TL, Spoorenberg A. A medical mystery -- arthritis. N Engl J Med 2006;354:2375-2375. [Free Full Text]

PDF PDA Full Text Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear Related Article by Jansen, T. L. PubMed Citation