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  1. Laboratory RoundsIs this a Septic Joint? Mark Boyko, R3 EM

  2. Case • 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

  3. Case • PMHx: • HTN • GERD • Smoker • Gout (toes, L ankle) – hasn’t had a flare in years • Meds • Allopurinol • Ramipril • Ranitidine

  4. Case • Phx • No fever, normal vitals • Knee looks swollen, no cellultis • Joint warm, ROM is painful but patient can do it

  5. Labs • Serum WBC 14 • ESR 32 • CRP 17 • Uric Acid 400 • Synovial Fluid • WBC 36 x109/L, PMN’s 65% • Low glucose • Negative for crystals

  6. Labs • Gram Stain • Negative What do you want to do??

  7. Overview • Value of serum labs • Value of synovial fluid analysis • Gram’s Stain & Cultures • Prosethetic Joints • Course of Action for Dry Taps

  8. Review – The Swollen Joint • Non-inflammatory • Trauma • OA • Inflammatory • RA • Crystal arthropathies • Seronegative arthropathies • Septic joint

  9. Why is this Important? • Joint destruction can occur within 2-3 days if untreated infection • Patients can become systemically septic from a joint infection rather easily • We need to make decisions before cultures come back

  10. We Love Prediction Tools • Can anything help us rule this out??

  11. Serum Labs • Serum WBC • >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

  12. Serum Labs • Serum ESR • ‘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

  13. Serum Labs • Serum CRP • ‘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

  14. Synovial Fluid • What’s Normal? • 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

  15. Synovial Fluid • Normal – amber, transparent

  16. Synovial Fluid • Inflammatory Cells - opaque

  17. Synovial Fluid • Hemarthrosis

  18. Hemarthrosis • Trauma #1 cause • Anticoagulation therapy • Hemophilia • Synovioma • Rarely, infection and hemarthrosis co-exist. If concerned, send for culture.

  19. Synovial Fluid

  20. Synovial Fluid • Glucose and Protein • 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

  21. Synovial Fluid • LDH • >250 U/L was 100% sensitive in retrospective study on 8 confirmed cases, prospectively was not as strong • Lactic Acid • 90-97% NPV, but low powered studies • Bottom Line: Insufficient data to date

  22. Synovial Fluid • Tumour Necrosis Factor –α • 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

  23. Synovial Fluid • WBC Margeretten et al, JAMA 2007

  24. Synovial Fluid • 30% of immunocompetent people with culture confirmed septic joint have synovial WBC <50 - McGillicuddy et al, Am J Emerg Med. 2007 • 50% of immunocompromised people with culture confirmed joint infection had WBC <28 -McCutchan et al, Clin Orthop Relat Res 1990

  25. Synovial Fluid • PMN’s Margeretten et al, JAMA 2007

  26. Synovial Fluid • WBC Bottom Line • 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

  27. Synovial Fluid • Eosinophilia • Parasitic infection • Allergy • Fungal • Neoplasm • Lyme disease

  28. Combined Value? • Li et al, Emerg Med J 2007 • Retrospective chart review 156 patients • Combined Sensitivity 100% if: • Serum WBC <11 • Serum ESR <20 • Synovial WBC <50 • Bottom Line: Not powered enough, not prospectively validated, cannot use to rule out septic joint

  29. Synovial Fluid • Crystals • Gout - Monosodium Urate, 90% sensitive, LR 14 • Pseudogout – PPDC, 80% sensitive, LR 2.6 • Cholesterol crystals – seen in chronic inflammatory conditions

  30. Crystals & Infection • Crystals do not rule out infection! • Retrospective study n=265 patients with crystals, 1.5% had septic joint -Shah et al, J of Emerg Med 2007 • Literature ranges from 1-20% of infectious joints co-exist with crystals

  31. Microbio Review • ALL AGES: #1 cause still Staph Aureus • <30, sexually active: Neisseria Gonorrhea • Elderly: Gram Negatives • Prosthetics: Careful of Pseudomonas

  32. Gram’s Stain • 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.

  33. Cultures • ‘Gold standard’ ? • Gonococcus difficult to culture • 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

  34. Gonococcal Arthritis • Synovial WBC often <50 • Gram stain Positive only 25% of the time • Culture Positive only 50% of the time • If you suspect it, culture at 3 mucosal sites (pharynx, genitals, anus)  will increase your chance of positive culture to 80% • Generally less destructive to the joint versus other pathogens

  35. Gram Stain Positive, Culture Negative • In reality, this is retrospective • Go with your Gram Stain  treat these patients while awaiting cultures • How does this happen? • Antibiotics already on board • Organism difficult to culture • Was infected, now clearing

  36. Prosthetic Joints • <3mos since surgery  likely Staph Epiderm • >3mos since surgery  Staph, Strep, Gram Neg • Should always call Ortho before tapping these in ER

  37. Prosthetic Joints • Trampuz et al, Amer J of Med 2004 • 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 • Retrospective n=86 knees • Ideal sensitivity 98% for synovial WBC 2.5 x109/L and PMN’s 60%

  38. What About Those Dry Taps?

  39. Dry Tap? • Makes a septic joint unlikely  usually a large enough effusion for tap, but never been validated • Options • 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

  40. Hot Joint, No Organism • Fastidious organism • Antibiotics begun before cultures sent • Wrong Diagnosis • Help increase your yield? • Use blood culture bottles for synovial fluid (aerobic and anaerobic) - Joint, Bone, Spine 2006

  41. Relevance to Pediatrics? • No good studies specifically on synovial fluid analysis in the pediatric population • Most use numbers from adult data

  42. How Many Use Kocher’s Criteria? Kocher et al, J of Bone Joint Surg 2004

  43. TAKE HOME MESSAGE • Cannot rely on serum values to rule out septic joint • If you believe there’s an effusion, get that fluid somehow • Unfortunately, nothing has a strong NPV

  44. TAKE HOME MESSAGE • Synovial fluid: WBC & PMN is helpful • WBC <18 is low risk but not zero • WBC >50 is high likelihood • PMN’S >90% is high likelihood • Glucose, Protein  useless

  45. TAKE HOME MESSAGE • ‘Gold Standard’ is clinical suspicion of an experienced physician, not laboratory tests (Current Opinion Rheumatology 2008) • Prosthetic Joints • Lower WBC & PMN threshold • Don’t feel bad - 30% of the time reason for effusion remains ‘unknown’

  46. Thanks • Feel free to ask for any references