Synovial Fluid Analysis Dx

Last updated: October 13, 2014

CPT Codes:  Polarized microscopy/Crystal ID 89060;  Cell count 89050

Description: Synovial fluid (SF) analysis is often used to aid differential diagnosis and therapy.  SF, the transudative product of type B synoviocytes, serves as a local lubricant and medium for nutrient replenishment to cartilage and other intraarticular structures. The primary goal of SF analysis is to discern whether a synovial effusion is noninflammatory, inflammatory, septic, or hemorrhagic.

Method: SF is primarily obtained by needle aspiration. A stepwise approach to joint aspiration and injection is detailed in Table 1. Joint fluid may also be obtained during other diagnostic and therapeutic procedures (i.e., arthrogram, arthroscopy, arthroplasty). SF usually will not clot but may with high fibrinogen levels (inflammatory states). Aspirated SF should be promptly divided among plain (red top) tubes (for glucose, if necessary), sodium (not lithium) heparin tubes (for crystals), EDTA (for cell count, differential, complement), or sterile culture tubes. If gonococcal arthritis is suspected, immediate inoculation on Thayer-Martin media is recommended. Delay in SF analysis may lower white blood cell (WBC) counts and increase the number of birefringent artifacts. Whereas the number of calcium pyrophosphate dihydrate (CPPD) crystals may decrease over time (i.e., weeks), monosodium urate (MSU) crystals will not. If the sample cannot be promptly analyzed, refrigerate at 4°C.

Crystal Analysis: A wet preparation requires only 1-2 drops of SF. Glass slides and coverslips should be clean and free of dust and other potentially birefringent debris. Crystals can been seen under plain light microscopy but are best seen under the polarizing microscope. Crystal identification is a highly sensitive and specific for certain diagnoses:
Gout: MSU crystals, seen in gouty effusions, are long, needle shaped, and negatively birefringent; they are usually intracellular during acute attacks. MSU crystals can be found in previously affected but currently quiescent joints.
Pseudogout: CPPD crystals, found in pseudogout and chondrocalcinosis, are usually shorter, rhomboid or needle shaped, and positively birefringent.
Cholesterol crystals: These appear as translucent “stacked panes of glass”.
Calcium oxalate crystals: These are positively birefringent and bipyramidal in shape.
Hydroxyapatite crystals: These are not routinely seen and may only be identified by electron microscopy or by staining with alizarin red.
Negative birefringence (i.e., MSU crystals): Present if the crystal appears yellow when parallel to the axis of the compensator and blue when perpendicular.
Positive birefringence (i.e., CPPD crystals): Present if the crystal appears blue when parallel to the axis of the compensator and yellow when perpendicular.

Table 1: Checklist for Arthrocentesis and Joint Injection
• Inform patient of purpose, expected benefits, and possible side effects of the procedure
• Document an informed consent to the procedure (verbal or written)
• Check for allergies: iodine, lidocaine, or adhesives
• Position patient to maximize patient comfort and joint exposure
• Identify bony landmarks with pen
• Identify puncture site with imprint from retracted end of ballpoint pen
• Wash hands before procedure and wear gloves (required by Occupational Safety Health Administration)
• Prepare and lay out syringes, needles and injectables (corticosteroid, anesthetic) to be used
• Cleanse injection site with povidone iodine solution
• Begin with topical anesthetic (i.e., ethyl chloride) and spray until a light frost appears
• Swab site with alcohol preparation
• Keep the injection site sterile
• Speak to patient throughout the procedure and inform of each step; pain may be felt while lidocaine is instilled (described as “burning”) or when needle penetrates an inflamed joint capsule or bursa (described as “sharp”)
• Use 22-, 23-, or 25-gauge needle for local anesthesia and joint injection
• Slowly infiltrate anesthetic (lidocaine) from surface to , pausing before each advance of the needle
• With each advance of the needle, draw back on the plunger before injecting
• Switch to an 18-gauge needle (or largest possible) if aspirating joint fluid
• Use hemostat to clamp and stabilize needle while changing syringes
• Use a 5- or 10-mL syringe to aspirate joint fluid; reposition needle if necessary
• Synovial fluid may not always be obtained once inside the joint; if large amount of fluid remains, leave needle in place, use 20- or 30-mL syringes to withdraw
• Once the return of aspirated SF ceases, a corticosteroid preparation, with or without a small amount of lidocaine, may be instilled into the joint, leaving the aspiration needle in place, stabilizing it with a hemo- stat, and changing syringes for steroid instillation
• Remove needle and apply local pressure for 2–4 min (longer if patients are on nonsteroidal antiinflammatory drugs, anticoagulants, or antiplatelet therapy)
• Process synovial fluid specimen promptly (i.e., laboratory workup, cultures, polarized microscopy)
• Record SF volume withdrawn, color, appearance, viscosity, microscopic findings, and tests ordered in the patient’s chart
• Advise home (bed/chair) rest and intermittently apply ice to the injected site (15-20 min ice packs every 2–3 h) for the 24–36 h after injection
• Immobilization for 24–72 h after injection may improve outcome
• Counsel patient to call or return if fever or local pain/erythema develops

Normal Values: Normal SF is transparent, clear, and colorless or pale straw colored. It is normally viscous, owing to high levels of hyaluronate. Expression of a drop of fluid from the syringe tip will produce a long, viscous, string-like tail (“string” sign). Viscosity, hyaluronate, and the string sign are lost with inflammatory states. Normal SF WBC counts are <200 cells/mm3, with a predominance of mononuclear cells. Normally, small amounts (5 mL) of joint fluid are present in large (i.e., knee) joints and smaller amounts may also be obtained from smaller (i.e., finger) joints. When available, SF should be examined for appearance, viscosity, and WBC count and differential. The clinician should determine the need for polarized microscopy, bacteriologic cultures, fungal cultures, and cytology. Whenever infection is suspected, SF should be Gram stained and cultured appropriately.

Not Recommended: SF protein, albumin, glucose, lactate dehydrogenase, complement, and serologic tests are of no diagnostic value in the analysis of SF. Nonetheless, protein, albumin, and complement levels are lower than serum values; the glucose concentration is normal and usually within 10 to 15 mg/dL of serum values.

Abnormal SF: SF is abnormal in a variety of conditions, including osteoarthritis, meniscal and cruciate tears, inflammatory arthritis (i.e., rheumatoid arthritis), crystal arthritis (i.e., gout), and hemorrhagic conditions. Table 2 details SF abnormalities and their disease associations. In noninflammatory conditions, SF WBC counts are between 200 and 2,000 cells/mm3. In inflammatory states, SF WBC counts range from 2,000 to 75,000 cells/mm3 and show a predominance of neutrophils. Septic effusions often have WBC counts ranging from 60,000 to 500,000 cells/mm3, with an even greater percentage of neutrophils. In most bacterially induced septic arthritides, SF has >90% neutrophils. SF WBC counts between 20,000 and 60,000 cells/mm3 may be seen in some infectious arthritides (i.e., gonococcal, fungal, tuberculosis) or previously treated (i.e., antibiotics) septic arthritis. Gouty effusions occasionally yield SF WBC counts >60,000 cells/mm3.


Table 2: Synovial Fluid Analysis
Noninflammatory Type I Inflammatory type II Septic Type III Hemorrhagic Type IV
Appearance Yellow Yellow Purulent Bloody
Clarity Clear Cloudy Opaque Opaque
VIscosity High Decreased Decreased Variable
Cell Count 200-2,000 2,000-75,000 >60,000 RBCs>>WBCs
(% PMNs) (<25% PMNs) (>50% PMNs) (>80% PMNs) Variable
Example Osteoarthritis, trauma, osteonecrosis, SLE RA, Reiter’s syndrome crystal arthritis SLE, viral arthritis, fungal arthritis, TB arthritis Bacterial arthritis, crystal arthritis Trauma, fracture, ligament tear, hemophilia, Charcot arthritis, PVNs
Abbreviations: RBCs, red blood cells; WBCs, white blood cells; PMNs, polymorphonuclear leukocyte; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus; TB, tuberculosis; PVNS, pigmented villonodular synovitis.

Indications: SF should be analyzed when available. Indications for arthrocentesis are given below.

Comment: With only a few drops of SF, the examiner can do a visual inspection, assess viscosity, and perform SF culture, polarized microscopy, and a peripheral smear to gauge the number and type of cells present. Crystal arthritis may coexist with septic arthritis or other inflammatory arthritides; however, coexistence of gout and rheumatoid arthritis is very rare.

Schmerling RH, Delbanco ML, Tosteson ANA, et al.Synovial fluid test: what should be ordered? JAMA 1990;264:1009–1014. PMID: 2198352
Maury EE, Flores RH.Acute monarthritis: diagnosis and management. Prim Care. 2006;33:779-93. PMID: 17088160

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