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Alpha Defensin Accuracy and Pitfalls in Diagnosing Septic Arthritis in Native Joints

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Alpha Defensin Accuracy and Pitfalls in Diagnosing Septic Arthritis in Native Joints 22 Acta Orthop. Belg., 2020,B.T.K .86 DING e-SUPPLEMENT, K.G. TAN, C2.,Y 22-25. KAU, M.F.B. MOHD FADIL ORIGINAL STUDY Alpha defensin accuracy and pitfalls in diagnosing septic arthritis in native joints Benjamin Tze Keong DING, Kelvin Guoping TAN, Chung Yuan KAU, Muhd Farhan bin MOHD FADIL From the Tan Tock Seng Hospital, National Healthcare Group, Singapore Purpose: This study aimed to test the accuracy of the INTRODUCTION synovial fluid biomarker, α-defensin, in diagnosing septic arthritis in native joints and highlight the Interest in utilizing intra-synovial fluid bio- pitfalls of its utilization for primary joints. We markers to diagnose Prosthetic Joint Infections also discuss the cases where false results were (PJI) has increased after synovial white blood demonstrated. cells (WBCs) were found to have unique gene Methods: A retrospective review of 10 patient’s expression profiles in response to bacterial infection records, who underwent α-defensin testing for (1). Deirmengian (3) screened 43 biomarkers based suspected primary joint infections prior to performing arthroplasty surgery, was performed. on previous studies and found 5 biomarkers; to be Results: 6 primary knee and 4 primary hip joints were 100% sensitive and specific for diagnosis of PJI evaluated for septic arthritis utilizing the α-defensin utilizing MSIS criteria. Defensins are antimicrobial test after arthrotomy was performed, as the patient peptides that are released by polymorphonuclear had turbid synovial fluid or atypical bony features cells (PMNs), monocytes and lymphocytes as part suggestive of septic arthritis. 2 of the primary hip of the innate immune system to neutralize invading joints had previous cephalomedullary nail insertions pathogens without prior sensitisation. that cut-out and 1 knee joint had previous distal femur The α-defensin test has, in numerous subsequent fixation for peri-articular fracture. There were 2 false studies, been found to have consistent sensitivity positive α-defensin results in native knee joints that and specificity, ranging from 95% to 100% (5), not were eventually attributed to inflammatory arthritis after extensive cultures and microbial sequencing results returned negative. All other patients had negative α-defensin results that correlated with anti- n Benjamin T. K. Ding1, MBBS (S’pore), MRCS (Edin). microbial testing. n Kelvin Guoping Tan1, MBBS (S’pore), MRCS (Edinburgh), Conclusion: The utilisation of the α-defensin test in M.Med (Ortho), FRCS Ed (Orth). primary joints should be interpreted with caution. n Kau Chung Yuan1, MBBS (S’pore), MRCS (Edinburgh), The elevated levels of α-defensin may be attributable M.Med (Ortho), FRCS Ed (Orth). n 1 to inflammatory arthritis and further studies of its Muhd Farhan Bin Mohd Fadil , MBBS (S’pore), MRCS levels in native joints are required. (Edinburgh), M.Med (Ortho), FRCS Ed (Orth). 1Department of Orthopaedic Surgery,Tan Tock Seng Keywords : Alfa defensin ; Joint infection ; Septic Hospital, 11 Jalan Tan Tock Seng, 308433, Singapore. Arthritis ; Periprosthetic Joint Infection ; Arthroplasty. Correspondence: Benjamin T. K. Ding, MBBS, MRCS, Singapore, Blk 78 Lorong Limau #35-79 S320078 ; Tel: +65 97936549. E-mail : [email protected] ©2020, Acta Orthopaedica Belgica. Level of evidence: Diagnostic IV, Study of Diagnostic Test. No benefits or funds were received in support of this study. The authors report no conflict of interests. No funding was Actautilized Orthopædica for the purposes Belgica, of thisVol. study.86 e-Supplement - 2 - 2020Acta Orthopædica Belgica, Vol. 86 e-Supplement - 2 - 2020 ALPHA DEFENSIN ACCURACY AND PITFALLS IN DIAGNOSING SEPTIC ARTHRITIS IN NATIVE JOINTS 23 affected by antibiotics or systemic inflammatory as the patient had turbid synovial fluid or atypical joint diseases and to respond to a wide variety bony features suggestive of septic arthritis. These of organisms including fungi (3,4). The test is included two primary hip joints which had had commonly utilized as a cassette embedded, visual previous cephalomedullary nail insertions that had immunochromatographic assay (Synovasure) that cut-out and 1 patient who had had previously distal can provide a diagnosis of PJI in 10 minutes. It is femur fixation complicated by subsequent aseptic increasingly being added to the armamentarium loosening. All three cases had true negative results. of the arthroplasty surgeon who may be interested Five other patients had negative α-defensin results to stretch the indications for its utilisation. The that correlated with anti-microbial testing. Two purpose of this study is to highlight the pitfalls of patients had severe avascular necrosis of the femoral its utilisation in native joints and discuss the factors head with severe collapse and end stage arthritis. that may lead to a false result. Three primary knees had atypical features of end stage arthritis. One patient had a valgus knee with METHODS severe arthritis, 1 patient had synovial overgrowth and 1 patient had turbid synovial suggestive of This study was approved by the Institutional infection. The patient profiles, comorbidities, surgical Review Board. A retrospective review of 10 indications, intraoperative findings and Synovasure cases of suspected joint infection that utilized the results are shown in Table I. Synovasure test (CD Diagnostics) between Nov There were two false positive α-defensin results 2015 and Nov 2017 was performed. Institutional in native knee joints that were eventually attributed review board approval was granted for this study to inflammatory arthritis after extensive cultures and patient’s clinical notes, operative records and and microbial sequencing results returned negative. perioperative radiographs were analysed. The 1st patient was a 54 year old Chinese gentleman All synovial fluid was collected preoperatively with a past history of refractory rheumatoid arthritis, or intraoperatively via needle aspiration or on Prednisolone and Cyclosporine. Previous after arthrotomy under aseptic conditions in therapies with sulphasalazine, hydroxychloroquine, the operating theatre. The synovial fluid was GOLD, Infliximab and adalimumab had failed. tested using the Synovasure (CD Diagnostic) test He was a Hepatitis B carrier on Lamivudine and which utilizes an enzyme-linked immunosorbent Adefovir for 18 years and suffered from ischaemic assay which defined 5.2mg/L as a positive result. heart disease post percutaneous intervention, Multiple fluid and tissue specimens were obtained hyperlipidemia, gastric polyps, colonic tubular and processed for full examination of microscopic adenomas and latent tuberculosis (TB), for which elements and bacterial cultures, 72 hours for he had completed 4 months of Rifampicin treatment aerobic cultures and 120 hours for anaerobic 8 years previously. He complained of worsening cultures. Patients with high suspicion of septic right knee pain over the past 6 months and was arthritis were further tested with bacteria genome only able to walk less than 1 bus stop on a level polymerase chain reaction (PCR) if initial results surface. He had had no recent fever or exacerbation returned negative and culture specimens were kept of his pain. He had had intra-articular injections of for an extended period of a week before disposal. hydrocortisone and lignocaine for pain relief, at 5 Patients were deemed to have septic arthritis if months and 15 months prior to surgery. Physical the cultures or polymerase chain reaction returned examination of his knee revealed minimal effusion positive. with mild warmth with range of motion from 10 to 100 degrees. Pre-operative total white cell count RESULTS was 14.9 x 109 per liter and radiographs of his right knee showed tricompartmental osteoarthritis Six primary knee and four primary hip joints with reduction in joint space, marginal osteophytes, were evaluated for septic arthritis with Synovasure, subchondral sclerosis and subchondral cysts. A Acta Orthopædica Belgica, Vol. 86 e-Supplement - 2 - 2020 24 B.T.K. DING, K.G. TAN, C.Y. KAU, M.F.B. MOHD FADIL Table I. — Summary of patient demographics, white cell count, intraoperative findings and synovasure results when used in native joints Patient Comorbidities Surgical Indication Pre-op White Intraoperative Findings Synovasure Cell Count Results (10^9/L) DM, HTN, HLD, Lt Breast Left Hip Cephalomedullary nail cut-out Negative 83/F Cancer Cephalomedullary Nail 8.2 Cut-out DM, HTN, HLD, Anaemia Right Distal Femur Distal femur plate fixation Negative 63/M 10.5 Fixation Failure loose. HTN, HLD, Gastric Ulcer Right Knee OA Valgus knee with severe Negative 47/M 7.4 arthritis HTN, Lung Asbestosis Left hip AVN Femoral head collapse with end Negative 74/M 9.4 stage arthritis HTN, HLD, Gout, Chronic Right knee OA Medial and lateral tibia condyle Negative 68/M Kidney Disease 8.9 wear and patella synovium overgrowth Previous Left Hip Osteomyelitis, Left hip AVN Femoral head collapse with end Negative 55/M 10.4 Psoas Abscess stage arthritis DM, HTN, HLD, Anaemia, Left knee OA Turbid synovial fluid Negative 60/M 5.3 Schizophrenia DM, HTN, HLD, Chronic Left Hip Cephalomedullary nail cut-out Negative 66/F Kidney Disease, Asthma, Cephalomedullary Nail 7.2 Multiple Myeloma Cut-out HLD, Rheumatoid Arthritis, Right knee Rheumatoid Turbid synovial fluid Positive 54/M Bronchiectasis, Hep B Carrier, Arthritis 11.6 Latent TB HTN, HLD, Inflammatory Left knee Inflammatory Synovium pale with turbid Positive Arthritis, Aortic Valve Arthritis synovial fluid 67/M 9.8 Regurgitation
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