Arthrocentesis - O'Rourke Pg 1 Approach to Aspiration and Injections ACR Virtual Rheumatology Practicum Jul 2020 Kenneth S. O'Rourke, MD Rheumatology Associates Portland, Maine Division Director Rheumatology Founding Member Carolinas Fellows Collaborative Arthrocentesis - O'Rourke Pg 2 Approach to Aspiration and Injections NB: This presentation will deal primarily with the technical aspects of injections. For a discussion on the indications and efficacy of these procedures, the learner may consider the following: • Roberts WN: Primer: pitfalls of aspiration and injection. Nat Clin Pract Rheum (2007) 3:464-72 • Philpose J, Baker K, O'Rourke KS, Deodhar A: Joint aspiration and injection: mastering the basics. J Musculoskel Med 28(6):216- 22,2011 (http://nwprimarycare.com/Journal%20Articles/joint%20aspiration%20&%20inj%20basics.pdf) • Evans CH et al: Progress in intra-articular therapy. Nat Rev Rheumatol (2014) 10:11-22 • Garg N et al: Intra-articular and soft tissue injections, a systematic review of relative efficacy of various corticosteroids. Clin Rheumatol (2014) 33(12):1695-706 • McAlindon TE et al: Effect of Intra-articular Triamcinolone vs Saline on Knee Cartilage Volume and Pain in Patients With Knee Osteoarthritis. A randomized clinical trial. JAMA (2017) 317:1967-75 I. What Comes Out A. Synovial fluid (tables adapted in part from Gatter RA, A Practical Handbook of Joint Fluid Analysis, Philadelphia: Lea & Febiger, 1984; see also Shmerling RH, et al: JAMA 264:1009-14, 1990, and Margaretten ME, et al: JAMA. 2007;297:1478-88) 1. Characteristics (note below in table: the rule of 2's) Normal Noninflammatory Inflammatory Septic Color transparent transparent translucent-opaque opaque Viscosity very high high low variable WBC/cubic mm < 200 200-2,000 > 2,000 > 50,000 % PMN < 75 (<25) < 75 (<25) > 75 (> 50) > 75 Examples OA, AVN, HOA RA, crystal, SpA bacterial CTDs, serum sickness infection; concentrated crystals; Estimating WBC: 1 WBC/hpf using 40x objective ~ 500 WBC/mm3 ‘pseudoseptic’ (eg RA, ReA, PsA) Hemorrhagic synovial fluid: trauma with or without fracture, Charcot joint, hemorrhagic diathesis, tumor Synovial fluid eosinophilia: infrequent, generally not associated with peripheral eosinophilia, and most cases had a benign course (Rheumatology 52:346-51, 2013) Synovial fluid in potential septic arthritis: Margaretten et al (JAMA. 297:1478-88, 2007) performed a meta-analysis of published articles to determine the accuracy and precision of clinical findings, including synovial fluid, for the diagnosis of monoarticular, nongonococcal bacterial arthritis. Prior to receiving the results of synovial fluid gram stain and culture, the synovial fluid WBC and %polys had the best utility to identify septic arthritis. The following table is adapted from their study: Summary Publications Sensitivity Specificity Likelihood Ratio (95% CI) Study Reviewed % % Positive Negative Synovial Fluid WBC >100k 4 29 99 28 (12-66) 0.71 (0.64-0.79) WBC >50k 4 62 92 7.7 (5.7-11) 0.42 (0.34-0.51) WBC >25k 4 77 73 2.9 (2.5-3.4) 0.32 (0.23-0.43) Polys > 90% 3 73 79 3.4 (2.8-4.2) 0.34 (0.25-0.47) Low glucose 3 51 85 3.4 (2.2-5.1) 0.58 (0.44-0.76) Protein >3 gm/dl 2 48 46 0.90 (0.61-1.3) 1.1 (0.76-1.6) LDH >250 U/L 2 100 51 1.9 (1.5-2.5) 0.10 (0.00-1.6) Serum WBC > 10k 1 90 36 1.4 (1.1-1.8) 0.28 (0.07-1.1) ESR > 30 mm/hr 1 95 29 1.3 (1.1-1.8) 0.17 (0.20-1.3) CRP > 100 mg/L 1 77 53 1.6 (1.1-2.5) 044 (0.24-0.82) Physical exam Fever 1 46 31 0.67 (0.43-1) 1.7 (1-3) Arthrocentesis - O'Rourke Pg 3 Synovial fluid in potential septic arthritis, prosthetic joint: Note that the synovial fluid WBC threshold levels for consideration of septic arthritis change when one is evaluating fluid aspirated from a prosthetic joint. Data in the table below, and a more detailed discussion on prosthetic joint infection can be found in: Tande AJ, Patel R: Prosthetic joint infection. Clin Microbiol Rev 2014; 27:302-345 Pubs Sens Spec Likelihood Ratio (95% CI) Rev’d % % Positive Negative Native Joint (JAMA 297: 1478-88, 2007) WBC >100k 4 29 99 28 (12-66) 0.71 (0.64-0.79) WBC >50k 4 62 92 7.7 (5.7-11) 0.42 (0.34-0.51) WBC >25k 4 77 73 2.9 (2.5-3.4) 0.32 (0.23-0.43) Polys > 90% 3 73 79 3.4 (2.8-4.2) 0.34 (0.25-0.47) Prosthetic Joint Knee (Am J Med 117: 556-62, 2004; PROSPECTIVE, n = 133, (aseptic 99, PJI 34), revision TKA) WBC > 1700 94 88 8.0 (5-13) 0.1 (0.0-0.3) WBC > 50k 21 100 (infinity) 0.8 (0.7-0.9) Polys > 65% 97 98 48 (12-190) 0.0 (0.0-0.2) Knee (J Bone Jt Surg Am 90: 1637-43, 2008; RETROSPECTIVE, n = 429, (aseptic 161, PJI 268), revision TKA) WBC > 1100 91 88 7.6 * 0.1 * Polys > 64% 95 95 17.9 * 0.1 * Hip (J Bone Jt Surg Am 90:1869-75, 2008; PROSPECTIVE, n=201 (aseptic 146, PJI 55) revision THA) WBC > 4200 84 93 12 * 0.2 * Polys > 80% 84 82 4.7 * 0.2 * *calculated Recent studies using test strips as an adjunct for suspecting septic arthritis: • Omar M et al (J Bone Joint Surg Am 2014; 96:2032) applied centrifuged synovial fluid supernatant from the joints of consecutive cases of atraumatic joint effusion presenting to an emergency department to the leukocyte esterase (LE) and glucose (GLC) test pads of a colorimetric strip that is usually used for urine analysis: Synovial fluid gram stain/culture were compared to the strip findings as noted below: LE ++ or +++ LE ++ or +++ and GLC − Sensitivity† (%) 94.7 (74.0 to 99.9) 89.5 (66.9 to 98.7) Specificity† (%) 73.2 (64.7 to 80.7) 99.2 (95.7 to 99.9) Positive predictive value† (%) 34.6 (22.0 to 49.1) 94.4 (72.7 to 99.9) Negative predictive value† (%) 98.9 (94.2 to 99.9) 98.4 (94.5 to 99.8) Positive likelihood ratio 3.54 114 Negative likelihood ratio 0.08 0.11 † estimate (95% confidence intervals) Arthrocentesis - O'Rourke Pg 4 • Mortazavi SMJ et al (J Pediatr Orthop 2019; epub) in a prospective study of children <18 yo suspected of hip or knee septic arthritis (n = 25), applied the supernatant from spun synovial fluid (acquired at operative arthrotomy or arthrocentesis) to the LE pad, and comparing results to synovial fluid gram stain/culture or the presence of purulent synovial fluid. A LE pad result of ++ or +++ had a positive likelihood ration of 5.88, and a negative likelihood ratio of 0. Utility of synovial fluid alpha-defensin in the evaluation of suspected septic arthritis • Others have looked at synovial fluid levels of alpha-defensin as an aid to diagnose infection, specifically prosthetic joint infection. The alpha-defensin protein is an antimicrobial peptide that is naturally released by neutrophils responding to a pathogen in the synovial fluid. (See Deirmengian C, et al: Clin Orthop Relat Res 2015; 473:198-203) 2. Crystal characteristics Crystal Brightness Morphology Size estimate/comments Negative birefringence MSU strong rod/needle, spherule up to 40 µm (maltese cross *) cholesterol weak plates (notched corners) 5-40 µm betamethasone strong rod 10-20 µm; confused with MSU acetate triamcinolone strong rod 15-60 µm; confused with MSU hexacetonide Positive birefringence CPPD weak rod, rhomboid up to 40 µm calcium oxalate variable/weak tetrahedron, rod lithium heparin weak polymorphic 2-5 µm nail polish strong rod 5-10 µm immersion oil strong polymorphic 1-5 µm prednisone TBA strong pleomorphic, branched confused with CPPD lipid inclusions in WBC maltese cross * liquid lipid maltese cross * talc maltese cross * Charcot-Leyden weak hexagonal bipyramid from crystallized eosinophil lysophospholipase (Arthritis Rheum 24:1591, 1981) Birefringent axis unclear methylprednisolone strong acetate triamcinolone strong acetate Cannot be seen with a compensated, polarized microscope Basic calcium phosphates (e.g., hydroxyapatite) * in MSU spherules, axis of the yellow triangles of cross are parallel with compensator axis; in talc and lipid, the blue triangle axis is parallel Arthrocentesis - O'Rourke Pg 5 Timing of synovial fluid evaluation for crystals • Synovial fluid must be evaluated promptly (within a couple of hours). Delay in fluid evaluation was been associated with a fall in synovial fluid WBC, fewer CPPD crystals (far more so than fall in MSU crystals), and the development of new crystal artifacts (Arthritis Rheum 32:271, 1989) • A more recent study (J Clin Rheumatol 19:241, 2013) suggested that crystal identification could be safely performed up to 3 days after arthrocentesis, whether synovial fluid (SF) was refrigerated (40C/39.20F) or at a stable room temperature (200C/680F). However, the 75 consecutive, uncentrifuged SF samples had to contain at least 5 mL (submitted native or in tubes with EDTA anticoagulant), and only 27 samples contained crystals (16 monosodium urate, 6 calcium pyrophosphate 5 both). Utility of centrifugation (cytospin technique) • Examination of synovial fluid sediment following centrifugation may enhance crystal detection (particularly CPPD crystals) by elevating cell and crystal count per high power field (Theiler G, et al: Rheumatol Int 34:137-139, 2014) B. Bursal fluid (table adapted from Zimmermann B, et al:Semin Arthritis Rheum 24:391, 1995, and Raddatz DA: J Rheumatol 14:1160, 1987): Nonseptic Septic bursal fluid WBC/cubic mm, range 90-11,000 350-395,000 %PMN 0-90 50-100 gram stain positive 0 15-100% C.