Laboratory Rounds
Is this a Septic Joint?
Mark Boyko, R3 EM
Case
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53 yo female comes in with 2 day history
of increasing R knee pain, now giving her
a limp. Does not recall injuring it
That knee is always ‘a little sore’ from
running injuries years ago
Case
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PMHx:
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HTN
GERD
Smoker
Gout (toes, L ankle) – hasn’t had a flare in years
Meds
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Allopurinol
Ramipril
Ranitidine
Case
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Phx
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No fever, normal vitals
Knee looks swollen, no
cellultis
Joint warm, ROM is
painful but patient can
do it
Labs
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Serum WBC 14
ESR 32
CRP 17
Uric Acid 400
Synovial Fluid
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WBC 36 x109/L, PMN’s 65%
Low glucose
Negative for crystals
Labs
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Gram Stain
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Negative
What do you want to do??
Overview
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Value of serum labs
Value of synovial fluid analysis
Gram’s Stain & Cultures
Prosethetic Joints
Course of Action for Dry Taps
Review – The Swollen Joint
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Non-inflammatory
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Trauma
OA
Inflammatory
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RA
Crystal arthropathies
Seronegative arthropathies
Septic joint
Why is this Important?
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Joint destruction can occur within 2-3 days
if untreated infection
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Patients can become systemically septic
from a joint infection rather easily
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We need to make decisions before
cultures come back
We Love Prediction Tools
 Can
anything help us rule this
out??
Serum Labs
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Serum WBC
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>10 x 109/L sensitivity of 50% for infection
LR 1.4
Many sterile but inflammatory joints give
elevated serum WBC
Bottom Line: Not sensitive
Serum Labs
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Serum ESR
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‘Elevation’ in most studies >30 mm/h
Sensitive but not specific
LR 1.3
Bottom Line: Only useful to track
resolution of the infection over time
Serum Labs
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Serum CRP
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‘Elevated’ in most studies >100 mg/L
Sensitivity 75%, poor specificity
LR 1.6
Bottom Line: Although CRP shows promise,
there is insufficient evidence for its sensitivity to
be high enough to rule out septic arthritis.
-Best Bets 2008
Synovial Fluid
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What’s Normal?
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Normal knee has avg 4cc synovial fluid
Normal synovial WBC <0.2x109/L
Glucose same as plasma
Uric Acid same as plasma
Protein <25% of plasma
Synovial Fluid
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Normal – amber, transparent
Synovial Fluid
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Inflammatory Cells - opaque
Synovial Fluid
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Hemarthrosis
Hemarthrosis
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Trauma #1 cause
Anticoagulation therapy
Hemophilia
Synovioma
Rarely, infection and hemarthrosis coexist. If concerned, send for culture.
Synovial Fluid
Findings
Normal
Non-Inflamm Inflammatory Septic
Colour
Clear
Yellow
Yellow
Yellow
Clarity
Transparent
Transparent
Opaque
Opaque
WBC (x109/L) <0.2
0.2 - 2
2 - 150
20 - 200
PMN’s
<25%
>50%
>75%
<25%
Synovial Fluid
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Glucose and Protein
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Synovial / Serum Glucose  <0.5-0.75, low
sensitivity
Synovial Glucose  <1.5 mmol/L sensitivity 38-64%
Synovial Protein  >25% of plasma, low sensitivity
Bottom Line: Glucose and Protein levels have
no role in the work up of a septic joint
Synovial Fluid
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LDH
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Lactic Acid
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>250 U/L was 100% sensitive in retrospective study
on 8 confirmed cases, prospectively was not as
strong
90-97% NPV, but low powered studies
Bottom Line: Insufficient data to date
Synovial Fluid
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Tumour Necrosis Factor – α
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Jeng et al, Am J Emerg Med 1997
Prospective, n=75
Synovial TNF-α >36.2 pg/mL sens 95%, spec
50% for bacterial infection
Bottom Line: Needs more study before
routine order
Synovial Fluid
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WBC
<25
LR 0.32
>25
LR 2.9
>50
LR 7.7
>100
LR 28.0
Margeretten et al, JAMA 2007
Synovial Fluid
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30% of immunocompetent people with
culture confirmed septic joint have
synovial WBC <50
- McGillicuddy et al, Am J Emerg Med. 2007
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50% of immunocompromised people
with culture confirmed joint infection had
WBC <28
-McCutchan et al, Clin Orthop Relat Res 1990
Synovial Fluid
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PMN’s
<90%
LR 0.34
>90%
LR 3.4
Margeretten et al, JAMA 2007
Synovial Fluid
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WBC Bottom Line
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Cut-off of 50 x109 /L too insensitive rule-out
infection
Use in clinical context
The diagnostic cut-off that maximized the
sensitivity / specificity was a synovial WBC
count of 17.5 x109/L (Sens 83%, Spec 67%)
- Li et al, Emerg Med J 2007
Synovial Fluid
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Eosinophilia
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Parasitic infection
Allergy
Fungal
Neoplasm
Lyme disease
Combined Value?
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Li et al, Emerg Med J 2007
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Retrospective chart review 156 patients
Combined Sensitivity 100% if:
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Serum WBC <11
Serum ESR <20
Synovial WBC <50
Bottom Line: Not powered enough, not
prospectively validated, cannot use to rule out
septic joint
Synovial Fluid
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Crystals
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Gout - Monosodium Urate, 90% sensitive, LR 14
Pseudogout – PPDC, 80% sensitive, LR 2.6
Cholesterol crystals – seen in chronic
inflammatory conditions
Crystals & Infection
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Crystals do not rule out infection!
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Retrospective study n=265 patients with
crystals, 1.5% had septic joint
-Shah et al, J of Emerg Med 2007
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Literature ranges from 1-20% of infectious
joints co-exist with crystals
Microbio Review
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ALL AGES: #1 cause still Staph Aureus
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<30, sexually active: Neisseria Gonorrhea
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Elderly: Gram Negatives
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Prosthetics: Careful of Pseudomonas
Gram’s Stain
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Guides your antibiotic therapy while awaiting
cultures
Need roughly 3-5cc for stain & culture
Only 65% sensitive for non-gonococcal
infections
Only 25% sensitive for gonococcal infections
Bottom Line: A negative Gram stain means
nothing. A positive Gram stain means you
should start treatment.
Cultures
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‘Gold standard’ ?
Gonococcus difficult to culture
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Negative 50% of the time
Requires chocolate agar
Non-gonococcus will culture 90% of time
If you only have enough fluid for one test, this is
what you do
Blood cultures reveal pathogen 25-50% of the
time
Gonococcal Arthritis
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Synovial WBC often <50
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Gram stain Positive only 25% of the time
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Culture Positive only 50% of the time
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If you suspect it, culture at 3 mucosal sites (pharynx,
genitals, anus)  will increase your chance of positive
culture to 80%
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Generally less destructive to the joint versus other
pathogens
Gram Stain Positive, Culture
Negative
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In reality, this is retrospective
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Go with your Gram Stain  treat these
patients while awaiting cultures
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How does this happen?
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Antibiotics already on board
Organism difficult to culture
Was infected, now clearing
Prosthetic Joints
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<3mos since surgery 
likely Staph Epiderm
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>3mos since surgery 
Staph, Strep, Gram Neg
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Should always call Ortho
before tapping these in ER
Prosthetic Joints
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Trampuz et al, Amer J of Med 2004
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Prospective, n=133, 34 had septic joint
Synovial WBC >1.7 x109/L , sens 94% spec 88%
Synovial PMN’s >65%, sens 97% spec 98%
Mason et al, J of Arthroplasty 2003
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Retrospective n=86 knees
Ideal sensitivity 98% for synovial WBC 2.5 x109/L and
PMN’s 60%
What About Those Dry Taps?
Dry Tap?
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Makes a septic joint unlikely  usually a large
enough effusion for tap, but never been
validated
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Options
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U/S guided in the department
Consult Ortho
Fluoroscopy guided
BOTTOM LINE: You need a sample of that fluid
if you are worried about infection
Hot Joint, No Organism
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Fastidious organism
Antibiotics begun before cultures sent
Wrong Diagnosis
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Help increase your yield?
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Use blood culture bottles for synovial fluid
(aerobic and anaerobic)
- Joint, Bone, Spine 2006
Relevance to Pediatrics?
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No good studies specifically on synovial
fluid analysis in the pediatric population
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Most use numbers from adult data
How Many Use Kocher’s Criteria?
Kocher et al, J of Bone Joint Surg 2004
TAKE HOME MESSAGE
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Cannot rely on serum values to rule out
septic joint
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If you believe there’s an effusion, get that
fluid somehow
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Unfortunately, nothing has a strong NPV
TAKE HOME MESSAGE
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Synovial fluid: WBC & PMN is helpful
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WBC <18 is low risk but not zero
WBC >50 is high likelihood
PMN’S >90% is high likelihood
Glucose, Protein  useless
TAKE HOME MESSAGE
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‘Gold Standard’ is clinical suspicion of an
experienced physician, not laboratory tests
(Current Opinion Rheumatology 2008)
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Prosthetic Joints
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Lower WBC & PMN threshold
Don’t feel bad - 30% of the time reason for
effusion remains ‘unknown’
Thanks
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Feel free to ask for any references