What is Glucose - Synovial Fluid?

When a patient presents with acute inflammatory monoarticular arthritis, aspiration of the involved joint is critical to rule out infectious arthritis and to attempt to confirm a diagnosis of gout or pseudogout on the basis of identification of crystals (see the image below). Minute quantities of fluid in the shaft or hub of the needle are sufficient for synovial fluid analysis.

Analysis of synovial fluid for crystals should ideally be done within 24-48 hours after collection. Synovial fluid specimens may be stored at room temperature without any preservative, but refrigeration (at 4°C/39°F) and ethylenediaminetetraacetic acid (EDTA) preservation are reasonable. A systematic literature review by Meyer et al found that monosodium urate (MSU) crystals were generally stable over time, independent of preservative and temperature, whereas calcium pyrophosphate (CPP) crystals deteriorated over time and were more stable if refrigerated. Re-examining an initially negative synovial fluid sample at 24 hours facilitated the detection of additional cases.

Urate crystals are shaped like needles or toothpicks with pointed ends (see the first image below). Under polarizing light microscopy, urate crystals are yellow when aligned parallel to the axis of the red compensator and blue when aligned across the direction of polarization (ie, they exhibit negative birefringence). Finding negatively birefringent urate crystals (see the second image below) firmly establishes the diagnosis of gouty arthritis.

Pseudogout crystals (CPP) are rod-shaped with blunt ends and are positively birefringent. Thus, pseudogout crystals are blue when aligned parallel to the slow ray of the compensator and yellow when they are perpendicular.

Crystals must be distinguished from birefringent cartilaginous or other debris. Debris may have fuzzy borders and may be curved, whereas crystals have sharp borders and are straight. As alkalization reduces uric acid crystal solubility and the enzyme uricase can “dissolve” these crystals, reduction by addition of sodium hydroxide or uricase to suspected gout crystal can be helpful. Corticosteroids injected into joints have a crystalline structure that can mimic either MSU or CPP crystals. They can be either positively or negatively birefringent.

The sensitivity of a synovial fluid analysis for crystals is 84%, with a specificity of 100%. If gout remains a clinical consideration after negative analysis findings, the procedure can be repeated in another joint or with a subsequent flare. Crystals may be absent very early in a flare.

Although the sensitivity of this test is inferior, aspiration of synovial fluid from previously inflamed joints that are not currently inflamed may reveal urate crystals. Such crystals are generally extracellular.

Synovial fluid should also be sent for cell count. During acute attacks, the synovial fluid is inflammatory, with a WBC count higher than 2000/µL (class II fluid) and possibly higher than 50,000/µL, with a predominance of polymorphonuclear neutrophils, though low WBC counts are occasionally found.

Synovial fluid glucose levels are usually normal, whereas they may be depressed in septic arthritis and occasionally in rheumatoid arthritis. Measurement of synovial fluid protein has no clinical value.

Crystalline arthritis and infectious arthritis can coexist. Indeed, infectious arthritis is more common in previously damaged joints, which may occur in patients with chronic gouty arthritis. Consequently, in patients with acute monoarticular arthritis, send synovial fluid for Gram stain and culture and sensitivity.

The pathologic specimens must be processed anhydrously. MSU is water-soluble and dissolves in formalin; therefore, only the ghosts of urate crystals may be seen if formalin is used. Absolute (100%) alcohol–fixed tissue is best for identification of urate crystals.

Once a diagnosis of gout is established by confirmation of crystals, repeat aspiration of joints with subsequent flares is not necessary unless infection is suggested or the flare does not respond appropriately to therapy for acute gout.