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Synovial fluid crystals and infection

16 min

  • Distinguish urate and CPP crystals by shape and compensated polarization
  • Recognize septic arthritis risk despite crystals or an overlapping cell count

Read the full reference

Try first

Try first

Short rhomboid crystals sit inside neutrophils in a knee fluid. With the red compensator in place, a crystal lying parallel to the slow axis is blue. Which crystal fits?

The next section explains it.

Right. The next section explains why.

The next section explains it.

The next section explains it.

Get the idea

Shape first, then the sign

Compensated polarized light is the main method for synovial crystals. Ordinary light finds the crystals and shows their shape. Crossed polarizers show which ones are birefringent, and the first-order red compensator shows the sign.1,2,3

FeatureMonosodium urate (MSU)Calcium pyrophosphate (CPP)
ShapeSlender needlesRhomboids or short rods
WhereFree or inside leukocytesOften inside leukocytes
Brightness under polarizersStrongWeak
Parallel to the slow axisYellowBlue
Across the slow axisBlueYellow

The color depends on how the crystal lies. Find the slow axis marked on the compensator, find a crystal lying along it, and then read the color. Yellow along the slow axis is negative birefringence and fits urate. Blue along the slow axis is positive birefringence and fits CPP. The report names the crystal and says whether it lies inside cells, outside them, or both.1,2

CPP crystals are weak and easy to miss, so a negative search cannot exclude CPP disease.1,3 Examine fresh fluid at room temperature. Refrigeration can grow crystals in the tube. Lithium heparin, oxalate and powdered EDTA can leave particles that look like crystals.1

Crystals and infection in the same joint

A synovial leukocyte count above 50,000/µL raises the chance of septic arthritis without proving it. A count below 25,000/µL lowers the chance, and infection is still possible. Counts run lower after antibiotics, early in infection and in patients with weak immune responses. Crystal arthritis and septic arthritis can occur in the same joint.4

The Gram stain misses many joint infections, so culture is the main way to find bacteria. When the volume is small, bacterial culture comes first, then the leukocyte count with its neutrophil percentage, then the crystal search.4 Finding crystals ends the crystal search and leaves the infection workup running.

References
  1. Jokic A, Milevoj Kopcinovic L, Culej J, Kocijan I, Bozovic M. Laboratory testing of extravascular body fluids: national recommendations on behalf of the Croatian Society of Medical Biochemistry and Laboratory Medicine. Part II: synovial fluid. Biochem Med (Zagreb). 2020;30(3):030501. doi:10.11613/BM.2020.030501
  2. Richette P, Doherty M, Pascual E, et al. 2018 updated European League Against Rheumatism evidence-based recommendations for the diagnosis of gout. Ann Rheum Dis. 2020;79(1):31-38. doi:10.1136/annrheumdis-2019-215315
  3. Abhishek A, Tedeschi SK, Pascart T, et al. The 2023 ACR/EULAR classification criteria for calcium pyrophosphate deposition disease. Arthritis Rheumatol. 2023;75(10):1703-1713. doi:10.1002/art.42619
  4. Ravn C, Neyt J, Benito N, et al. Guideline for management of septic arthritis in native joints (SANJO). J Bone Jt Infect. 2023;8:29-37. doi:10.5194/jbji-8-29-2023

Watch one

A fresh knee fluid arrives at room temperature, 20 minutes after aspiration. A wet preparation goes under the microscope. What crystal is present?

  1. In ordinary light, find the crystals: slender needles, some inside neutrophils and some free.

    Shape narrows the choice before any color is read.

  2. Cross the polarizers: the needles glow brightly against the dark field.

    Urate shines strongly under crossed polarizers, and CPP is faint.

  3. Insert the red compensator and note its slow axis, marked on the plate as running from lower left to upper right.

    A color means nothing until the slow axis is known.

  4. Find a needle lying along the slow axis: it is yellow.

    The sign is read from a crystal lying along the slow axis.

  5. Check a needle lying across the slow axis: it is blue.

    A second orientation confirms the sign.

  6. Name the crystal and where it lies: monosodium urate, inside and outside cells.

    Yellow along the slow axis is negative birefringence, and strong negative needles are urate.

Monosodium urate crystals, intracellular and extracellular, with strong negative birefringence.

Your turn

Problem 1 of 3

Synovial needles are yellow when parallel to the compensator's slow axis and blue when perpendicular. Which crystals fit?

Incorrect. Calcium pyrophosphate (CPP) crystals show weak positive birefringence, blue when parallel to the slow axis and yellow when perpendicular, and they form rhomboids or short rods.

Incorrect. Calcium oxalate forms birefringent bipyramids or envelope shapes and can appear with oxalosis or advanced kidney disease.

Correct. Yellow parallel and blue perpendicular to the slow axis is strong negative birefringence, and with a needle shape it identifies monosodium urate (MSU), which supports gout.

Hint
  1. Start with the color of a needle lying along the slow axis.
  2. Decide whether yellow along the slow axis is the positive or the negative sign.

Review Crystal examination

Problem 2 of 3

This locating view shows a urate field. The arrow beside it marks the slow axis, running from lower left to upper right. Point to the needle whose long axis lies closest to the slow axis.

The locating view of a synovial fluid field with monosodium urate needles among neutrophils, and an arrow beside it marking the slow axis of the compensator.
  1. Needle at the lower left
  2. Needle at the upper right
  3. Needle near the middle
  4. Needle below the middle
Hint
  1. Find the arrow beside the picture before looking at any needle.
  2. Judge each needle by the direction of its long axis, and leave its color for last.
Show the answer

Yellow needle at the lower left

The yellow needle at the lower left runs from lower left to upper right, along the slow axis. Urate along the slow axis is yellow, the negative sign. The blue needles lie at wide angles to the slow axis, and the one at the upper right lies straight across it.

Review Crystal examination

Problem 3 of 3

A knee fluid from a patient who started antibiotics two days ago has 18,000 leukocytes/µL with 85% neutrophils. No crystals are seen, and the Gram stain shows no organisms. What do the results show about infection?

A count below 25,000/µL lowers the chance of infection, and antibiotics push counts down further. Infection is still possible.

No neutrophil percentage separates infection from other inflammation. The results support inflammation and name no cause.

Antibiotics lower the count and the chance of a positive Gram stain. Culture remains the main way to find bacteria in the joint.

Review Cell patterns in joint disease

Use it

  • Harold Brandt, 67, MRN 3318402, has a hot, swollen knee.
  • The aspirate is 0.8 mL in one sterile syringe. It arrives at room temperature 25 minutes after collection.
  • The requisition asks for a cell count, a crystal search, a Gram stain and culture.
Decision 1 of 3

Which aliquot comes first when the 0.8 mL is divided?

Culture is the main way to find bacteria, and it needs fluid that stays sterile. The count and crystal search share what remains.

Crystals do not rule out infection. When the volume is small, bacterial culture comes first.

The count overlaps between crystal arthritis and infection, so it cannot decide that culture is unnecessary.

Review Cell patterns in joint disease

Decision 2 of 3

Bright needles lie inside neutrophils. A needle lying across the slow axis of the compensator is blue. Which crystal is it?

CPP is blue only when it lies along the slow axis. This needle lies across it, and CPP forms faint rhomboids.

Assigned the birefringence sign without checking orientation

The compensator color depends on the crystal's orientation to the slow axis. Urate needles are yellow when parallel and blue when perpendicular, and calcium pyrophosphate (CPP) crystals show the reverse. Reading a color without the orientation can swap the sign and report CPP as urate or urate as CPP.

Blue across the slow axis means yellow along it, the negative sign. Bright negative needles are urate.

Steroid crystals are variable plates or shards, and nothing in the history mentions an injection. These are needles with a clear negative sign.

Review Crystal examination

Decision 3 of 3

The count is 54,000 leukocytes/µL with 92% neutrophils, and the Gram stain shows no organisms. How are the results reported?

Urate and bacteria can share a joint, and a count this high overlaps both. The comment could stop a workup that the culture still has to finish.

Ended the infection workup after finding crystals

Crystal arthritis and septic arthritis can occur in the same joint, and their cell counts overlap. Stopping at the crystal finding can leave a septic joint without the culture that identifies it.

The count, crystals and stain are accurate now. Waiting days for the culture delays results the clinician needs today.

Each result is reported as found. The culture stays open because crystals and infection can occur together.

Review Cell patterns in joint disease

The clue that settled this case is the small volume with infection on the requisition. The sterile aliquot went first, the urate needles were named by their sign along the slow axis, and the crystals left the culture running.

Keep

Sources checked