Transcript Synovial fluid analysis - Department of Medicine

Synovial fluid
analysis
PHILIP CHUI
NATHAN KING
MIRIAM NOJAN
STEVEN ZHAO
AMBULATORY PRESENTATION
OCTOBER 16, 2015
Introduction
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Synovial fluid
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Viscous, non-Newtonian fluid (variable viscosity)
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Reduce friction between joints during movement
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Filtered plasma with hyaluronic acid and lubricating glycoproteins
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Obtained mostly for patients with bacterial infections or crystal-induced
synovitis
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Only one to two ml of fluid needed for analyses
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Normal knee only with 3-4ml of fluid
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Uric acid and glucose levels in synovial fluid same as that of plasma
Indications
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Suspected septic arthritis
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Any febrile person with unexplained inflammatory fluid -> presumed septic joint
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Even with acute flare of arthritis (e.g., RA), should rule out septic joint
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Need to have low threshold to suspect infected joint as irreversible joint
destruction occurs rapidly
Suspected crystal-induced arthritis
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Gout or pseudogout diagnosis largely made with microscopic examination
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Diagnosis requires negative Gram stain/culture
Unexplained joint or bursa swelling
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Largely to permit classification into inflammatory vs noninflammatory categories
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Diagnosis made along with history & physical
Categories of synovial fluid findings
Measure
Normal
Noninflammatory
Inflammatory
Septic
Hemorrhagic
Volume, ml
<3.5
Often >3.5
Often >3.5
Often >3.5
Usually >3.5
Clarity
Transparent
Transparent
Translucentopaque
Opaque
Bloody
Color
Clear
Yellow
Yellow to clear
Yellow/green
Red
Viscosity
High
High
Low
Variable
Variable
WBC/mm3
<200
0-2,000
2,000-100,000
15,000->100,000
200-2000
% PMN
<25
<25
>50
>75%
50-75
Culture
Negative
Negative
Negative
Often positive
Negative
Synovial fluid findings examples
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Noninflammatory
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Degenerative joint disease
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Trauma
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Osteochondritis dissecans
Inflammatory
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RA, reactive arthritis, ankylosing spondylitis, psoriatic arthritis
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Acute crystal-induced synovitis
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SLE, rheumatic fever, sarcoidosis, scleroderma (these also can present as noninflammatory)
Septic (>100,000 WBC/mm
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Bacterial
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Myobacterial
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Fungal
3
not always septic)
Hemorrhagic
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Hemophilia
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Hemorrhagic diathesis
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Trauma
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Neoplasms
Data for cell count for diagnosis
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Cell count
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Positive likelihood ratio of septic arthritis from 2007 meta-analysis
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>25,000/mm3  2.9
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>50,000/mm3  7.7
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>100,00/mm3  28
Low cell count (<20,00/mm3) helpful with ruling out septic arthritis
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Positive LR (0.32).
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Can be low in immunocompromised patients, mycobacterial or some Neisserial and
some gram positive organisms
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Nucleated cell differential helps more with negative predictable value
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Eosinophils in synovial fluid suggests parasites, Lyme, cancer, or allergy
Margaretten et al. Does this adult patient have septic arthritis? JAMA. 2007;297(13):1478.
Gram stain/culture
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Useful for rapid assessment of synovial fluid but with poor sensitivity
(50-70%) – especially for gonococcal arthritis (<10%)
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Positive cultures are the gold standard for septic arthritis but can
often be negative, especially for gonococcal arthritis
Shmerling. Synovial fluid analysis. A critical reappraisal. Rheum Dis Clin North Am. 1994;20(2):503.
Crystal induced arthropathies
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Gout: monosodium urate crystals, needle shaped, negatively
birefringent (yellow)
Crystal induced arthropathies
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Pseudogout: calcium pyrophosphate dihydrate (CPPD) crystals,
rhomboid shape, positive birefringent (blue)
Data for crystal analysis for
diagnosis
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Gout/MSU crystals
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Sensitivity 63-78%, specificity 93-100%, LR+ 14
Pseudogout/CPPD crystals – harder to detect!
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Sensitivity 12-83%, specificity 78-96%, LR+ 2.9
Swan et al. The value of synovial fluid assays in the diagnosis of joint
disease: a literature survey. Ann Rheum Dis. 2002;61(6):493.
Key points
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Arthrocentesis yields a lot of useful information and should be
considered early in the evaluation of an inflamed joint, particularly if
there is concern for septic arthritis.
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The wbc count will often be the first point of differentiation between
non-inflammatory, inflammatory, and infectious arthritis
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Microscopic examination provides further clues via Gram stain and
crystal evaluation
Question 1
A 47-year-old man is evaluated in the emergency department for a 5-day history of
acute swelling and pain of the right knee. He has a 15-year history of gout, with
multiple attacks annually; he also has diabetes mellitus and chronic kidney disease.
Medications are enalapril, glipizide, and allopurinol.
On physical examination, temperature is 38.2 °C (100.8 °F), blood pressure is 146/88 mm
Hg, pulse rate is 96/min, and respiration rate is 15/min. BMI is 27. Several nodules are
noted on the metacarpophalangeal and proximal interphalangeal joints and within
the olecranon bursa. The right knee is swollen, erythematous, warm, tender, and
fluctuant.
Question 1
Laboratory studies:
Hemoglobin 10.1 g/dl
Leukocyte count 13,000/micro liter
(85% Neutrophils)
Serum Creatinine 2.8 mg/dl
Serum Uric Acid 9.2 mg/dl
Radiographs of the knee reveal soft-tissue swelling.
Aspiration drainage of the right knee is performed. Synovial fluid leukocyte count is
110,000/µL ([110 × 109/L], 88% neutrophils). Polarized light microscopy of the fluid
demonstrates extracellular and intracellular negatively birefringent crystals. Gram
stain is negative for bacteria. Culture results are pending.
Question 1
Which of the following is the most appropriate initial treatment?
A. Intra-articular methylprednisolone
B. Prednisone
C. Surgical debridement and drainage
D. Vancomycin plus piperacillin-tazobactam
Question 1
Which of the following is the most appropriate initial treatment?
A. Intra-articular methylprednisolone
B. Prednisone
C. Surgical debridement and drainage
D. Vancomycin plus piperacillin-tazobactam
Question 1 Explanation
Key Point: Bacterial infectious arthritis and gout can occur concomitantly in the same joint and should
be suspected when there is a very high (>50,000/µL [50 × 109/L]) synovial fluid leukocyte count..
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Given hx of gout, the presence of tophi, and intracellular and extracellular negatively birefringent
(urate) crystals, the patient is currently having a gout attack. However, high synovial fluid WBC
(>50,000/µL [50 × 109/L]) requires acute joint process be presumed infectious until proved otherwise.
Empiric therapy with vancomycin plus piperacillin-tazobactam, pending the results cultures.
Chronic joint damage leads to greater risk for joint infection. This patient also has diabetes mellitus
and is presumed to be immunocompromised and susceptible not only to gram-positive, but also to
gram-negative and anaerobic, organisms. Therefore, empiric combination therapy with
vancomycin and piperacillin-tazobactam is an appropriate approach.
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Although intra-articular methylprednisolone is an appropriate approach to treat an acute gout
attack while minimizing systemic corticosteroid effects, corticosteroids should never be injected
into potentially infected joints.
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Prednisone is also an effective treatment for acute gout, particularly if polyarticular; however, use
in this patient with diabetes and a potential joint infection would not be justifiable unless and until
infection were ruled out.
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In this patient, infection has not been proven, and the joint has been drained. Surgical
debridement and drainage can be considered for a definitively infected joint, particularly if the
percutaneous approach is inadequate to fully drain the entire joint, but is premature at this time.
Question 2
A 68-year-old woman is evaluated in the emergency department for a 2-day history of
swelling of the right knee. She has an 8-year history of right knee osteoarthritis. She
also has chronic kidney disease, hypertension, type 2 diabetes mellitus, and a history
of peptic ulcer disease. Medications are metformin, omeprazole, enalapril, and
aspirin.
On physical examination, temperature is 37.0 °C (98.6 °F), blood pressure is 132/84 mm
Hg, pulse rate is 78/min, and respiration rate is 14/min. BMI is 22. On musculoskeletal
examination, the right knee is swollen, warm, tender, and erythematous, with limited
range of motion. There are no tophi.
Question 2
Laboratory studies reveal an erythrocyte sedimentation rate of 49 mm/h, a serum
creatinine level of 2.1 mg/dL (185.6 µmol/L), and a serum uric acid level of 4.5 mg/dL
(0.27 mmol/L).
Aspiration of the right knee is performed. Synovial fluid leukocyte count is 25,000/µL (25
× 109/L), with 85% neutrophils. Polarized light microscopy of the fluid demonstrates
numerous positively birefringent crystals seen both extracellularly and within the
neutrophils.
Radiographs of the right knee reveal soft-tissue swelling and bilateral medial joint-space
narrowing, with linear calcific densities within the plane of the cartilage. Synovial fluid
Gram stain is negative for bacteria.
Question 2
Which of the following is the most appropriate treatment?
A. Allopurinol
B. Indomethacin
C. Intra-articular triamcinolone
D. Intravenous vancomycin
E. Prednisone
Question 2
Which of the following is the most appropriate treatment?
A. Allopurinol
B. Indomethacin
C. Intra-articular triamcinolone
D. Intravenous vancomycin
E. Prednisone
Question 2 Explanation
Key Point: Treatment of a patient with acute pseudogout is directed exclusively toward relieving
the inflammation using NSAIDs, intra-articular or systemic corticosteroids, or colchicine.
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Intra-articular triamcinolone is advantageous for this patient. She has intra-articular,
intracellular, and extracellular positively birefringent rhomboid-shaped (calcium
pyrophosphate) crystals, of acute pseudogout. Linear calcium deposits in the cartilage
(chondrocalcinosis), also supports the diagnosis of CPPD. Treatment is directed exclusively
toward relieving the inflammation and is tailored to the individual patient. This patient's
diabetes mellitus, chronic kidney disease, and history of peptic ulcer disease make local
therapy with an intra-articular corticosteroid the most desirable option.
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Oral allopurinol is a urate-lowering strategy for patients with established gout.
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NSAIDs such as Ibuprofen (not typically Indomethacin) are useful in acute attack of
pseudogout; however, this patient has numerous comorbid illnesses, all of which may be
exacerbated by NSAIDs.
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Established pseudogout diagnosis, negative Gram stain and a moderately low (inflammatory)
synovial WBC(<50,000/µL [50 × 109/L]) make an infection unlikely. Thus IV Vanco is not
indicated.
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Administration of a tapering dose of prednisone could be effective in treating this patient's
pseudogout attack but would be undesirable owing to her diabetes.
Question 3
A 58-year-old man is evaluated for acute onset of warm swollen right ankle of 3 days
duration. He had a similar episode 2 years ago involving his left great toe that
resolved in 5 days. He is otherwise healthy and on no medications.
On Physical exam Temperature is 98.0 F, BP 140/90, HR 80, and RR 12. Abnormal findings
are limited to a warm swollen right ankle with painful painful passive range of motion.
An arthrocentesis is performed. Synovila fluid cell count is 30,000/microliter, with 95%
polymorphonuclear cells and 5% lymphocytes. Gram stain does not indicate
bacteria.
Question 3
Polarized Light Microscopy
Direction of Polarized beam
Question 3
Which of the following is the most appropriate treatment?
A. Allopurinol
B. Colchicine
C. Febuxostat
D. Indomethacin
Question 3
Which of the following is the most appropriate treatment?
A. Allopurinol
B. Colchicine
C. Febuxostat
D. Indomethacin
Question 3 Explanation
Key Point: NSAID therapy is important for acute pain relief in an acute gouty attach
corticosteroids and colchicine also important in the acute treatment of gout.
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After identification of monosodium urate crystals on arthrocentesis or aspiration of
tophus the immediate treatment of the pain of gout attack with NSAIDs. Caution in
elderly, renal impairment, bleeding, or ulcer disorders.
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Monosodium urate crystals are needle-shaped and yellow when parallel to polorized
light.
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Cortocosteroids therapy is effective as oral, intravenous or intra-articular therapy of an
acute gouty attack
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Colchicine should be used in first 24 hours of symptoms and may abort attacks. It can be
given two or three times a daily until patient expericnes symptomatic relief, develops
gastrointestinal toxicity, or reaches max dose of 6mg per attack.
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Allopurinol and feboxostat are xanthine oxidase inhibitors used to reduce uric acid levels
and reduce recurrent attacks. Acute decreases in uric acid level may prolong current
attac or precipitate new attacks. Prophylactic colchicine, low-dose corticosteroids, or
NSAIDs initiated at least 1 week prior to initiation of allopurinol may prevent disease flares
associated with initiation of therapy.
Question 4
A 72-year-old woman is evaluated in the emergency department for severe right
shoulder pain and swelling. Three weeks ago, she injured her shoulder when falling
from a stepladder and went to the emergency department; radiographs of the
shoulder revealed soft-tissue swelling. She partially improved, but the pain and
swelling recurred after several days and gradually worsened. She has been taking
acetaminophen for the pain, with no relief.
On physical examination, temperature is 37.1 °C (98.8 °F), blood pressure is 116/76 mm
Hg, pulse rate is 78/min, and respiration rate is 14/min. BMI is 23. The right shoulder is
swollen, erythematous, warm, and tender, particularly over the anterior surface.
Range of motion of the shoulder elicits pain and is limited.
Question 4
Radiographs of the right shoulder reveal significant soft-tissue swelling and
possible large fluid collection. There is a hazy overlay of calcification
around the entire joint, and the joint itself is eroded.
Aspiration of the right shoulder is performed; the fluid is blood tinged. Synovial
fluid leukocyte count is 32,000/µL ([32 × 109/L], 82% polymorphonuclear
cells). Polarized light microscopy reveals no needle- or rhomboid-shaped
crystals. Gram stain and cultures are negative.
Question 4
Which of the following is the most likely diagnosis?
A. Basic calcium phosphate deposition disease
B. Calciphylaxis
C. Calcium pyrophosphate deposition disease
D. Osteoarthritis
Question 4
Which of the following is the most likely diagnosis?
A. Basic calcium phosphate deposition disease
B. Calciphylaxis
C. Calcium pyrophosphate deposition disease
D. Osteoarthritis
Question 4 Explanation
Key Point: Basic calcium phosphate crystals are commonly associated with chronic and highly
destructive inflammatory arthritis such as Milwaukee shoulder.
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This patient most likely has basic calcium phosphate (BCP) deposition disease, a crystal disease that
should be considered in older persons, especially women, and in the setting of trauma. BCP crystals
are most commonly associated with highly destructive inflammatory arthritis such as Milwaukee
shoulder, which typically manifests as shoulder pain and a large noninflammatory effusion that may
be bloody, often appearing subsequent to trauma. Active motion is markedly limited because of
the destruction of articular cartilage and associated tendon structures that develop in this setting,
whereas passive motion may be preserved. This patient has an erosive arthritis that developed
subacutely subsequent to a trauma; the presence of periarticular diffuse calcification is most
consistent with Milwaukee shoulder. Radiographs commonly show both articular and periarticular
calcification. BCP crystals cannot be seen under polarized light microscopy but can be visualized
as aggregates after alizarin red staining of synovial fluid (although not done routinely), which can
confirm the clinical diagnosis.
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Calciphylaxis is a condition of soft-tissue calcification that does not typically involve joints and
occurs almost exclusively in patients with stage 5 chronic kidney disease.
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Calcium pyrophosphate crystals can produce an acute, inflammatory arthritis. In contrast to BCPinduced disease, periarthritis is not a typical feature. Joint fluid examination under polarized light
microscopy shows many leukocytes (largely neutrophils) and intra- and extracellular positively
birefringent crystals.
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Osteoarthritis can affect the shoulder but is typically a chronic rather than acute problem. The joint
fluid tends to be noninflammatory, with a leukocyte count of less than 2000/µL (2.0 × 109/L).