G Model BONSOI-4152; No. of Pages 2
ARTICLE IN PRESS Joint Bone Spine xxx (2015) xxx–xxx
Available online at
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Letter to the editor The detection of monosodium urate crystals in synovial fluid after long-term and varying storage conditions
a r t i c l e
i n f o
Keywords: Gout Monosodium urate crystals Diagnosis Synovial fluid storage
The gold standard for diagnosing gout is the identification of monosodium urate (MSU) crystals in synovial fluid by polarisation light microscopy (PLM) [1,2]. Most often, however, gout is diagnosed without this preferable gold standard, e.g. at emergency departments or in primary care, where PLM is not easily accessible. On contrary, PLM could be more widely used if knowledge would dictate that immediate analysis of synovial fluid is no necessity. To allow delayed assessment of MSU crystals the presence of such crystals should be stable to withstand sample storage and transportation [3,4]. The aim of this study was to determine the ability to detect MSU crystals after long-term storage at different temperatures. Synovial fluid aspirates of at least 1.2 mL (baseline) of 10 patients were collected at the rheumatology department of Rijnstate Hospital, The Netherlands, and were analyzed by experienced synovial fluid assessors (LK and MJ) for the presence of MSU crystals with PLM. Every aspirate with MSU crystals present at baseline was divided over 30 cuvets of at least 40 L each. Ten cuvets were stored at −20 ◦ C, 4 ◦ C and room temperature, respectively. No anticoagulant or preservative was added. All samples were re-analyzed by the same assessors for the presence of MSU crystals pseudo-randomly at several time-points until week 24. The Fig. 1 shows that detection of MSU crystals was still possible in the majority of synovial fluid samples, even after 24 weeks of storage. The total mean percentages of samples with re-identified MSU crystals present were 87, 69, and 89% in the −20 ◦ C, 4 ◦ C, and 20 ◦ C groups, respectively. The number of evaporated samples was the largest in the 20 ◦ C group. The presence of MSU crystals upon repetitive assessments over time was variable, which might be due to intra- and interobserver variability, and difference in the concentration of MSU crystals per sample. Our results are partially in accordance with the literature. In a systematic review of Graf et al., 5 studies [3–7] were analyzed concerning storage in synovial fluid of gout patients [8]. MSU crystals remained stable in synovial fluid stored at room temperature for 24–72 hours [4,5,9]. After this time period, the amount of MSU crystals decreased. Storage at 4 ◦ C slowed this process, and after 8 weeks in all patients MSU crystals could be identified [4]. We did
Fig. 1. The presence of MSU crystals in stored synovial fluid samples at three different temperatures. 5 samples of knee joints and 5 samples of ankle joints were included. In patient 7, MSU crystals were re-identified in every sample. Although in patients 4 and 5 MSU crystals were often not re-identified, they were re-assessed at every temperature at least once.
not study the amount of MSU crystals. However, our results did not show that more MSU crystals were re-identified after storage at 4 ◦ C compared to storage at 20 ◦ C. Our results agree with the literature that anticoagulation was not required [3]. And we show that not only dried cytospin preparations allowed long-term storage and delayed analysis [7], but also synovial fluid stored without any specific conservation process. Altogether, this study underscores that synovial aspirates can be stored for delayed analysis with PLM to detect MSU crystals. This could increase the availability of synovial fluid analysis to improve the validity of the diagnosis of gout at emergency departments and in primary care, when the facilities are not easily accessible. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. References [1] Wallace SL, Robinson H, Masi AT, et al. Preliminary criteria for the classification of the acute arthritis of primary gout. Arthritis Rheum 1977;20:895–900. [2] Zhang W, Doherty M, Pascual E, et al. EULAR evidence based recommendations for gout. Part I: diagnosis. Report of a task force of the Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis 2006;65:1301–11. [3] Galvez J, Saiz E, Linares LF, et al. Delayed examination of synovial fluid by ordinary and polarised light microscopy to detect and identify crystals. Ann Rheum Dis 2002;61:444–7. [4] Kerolus G, Clayburne G, Schumacher Jr HR. Is it mandatory to examine synovial fluids promptly after arthrocentesis? Arthritis Rheum 1989;32:271–8. [5] Bible MW, Pinals RS. Late precipitation of monosodium urate crystals. J Rheumatol 1982;9:480. [6] de Medicis R, Dansereau JY, Menard HA, et al. [Diagnosis of gout: problems caused by crystallization “in vitro” of sodium urate]. Union Med Can 1979;108:810 [2, 4 passim].
http://dx.doi.org/10.1016/j.jbspin.2014.10.020 1297-319X/© 2015 Published by Elsevier Masson SAS on behalf of the Société Française de Rhumatologie.
Please cite this article in press as: Kienhorst LBE, et al. The detection of monosodium urate crystals in synovial fluid after long-term and varying storage conditions. Joint Bone Spine (2015), http://dx.doi.org/10.1016/j.jbspin.2014.10.020
G Model BONSOI-4152; No. of Pages 2 2
ARTICLE IN PRESS Letter to the editor / Joint Bone Spine xxx (2015) xxx–xxx
[7] Robier C, Neubauer M, Stettin M, et al. Dried cytospin preparations of synovial fluid are a stable material for long-time storage and delayed crystal analysis. Clin Rheumatol 2012;31:1115–6. [8] Graf SW, Buchbinder R, Zochling J, et al. The accuracy of methods for urate crystal detection in synovial fluid and the effect of sample handling: a systematic review. Clin Rheumatol 2013;32:225–32. [9] Tausche AK, Gehrisch S, Panzner I, et al. A 3-day delay in synovial fluid crystal identification did not hinder the reliable detection of monosodium urate and calcium pyrophosphate crystals. J Clin Rheumatol 2013;19: 241–5.
Laura B.E. Kienhorst a,∗ Hein J.E.M. Janssens b,c Roelant S. Eijgelaar d Tim R.D.J. Radstake e Piet L.C.M. van Riel f Matthijs Janssen a a Department of Rheumatology, Rijnstate Hospital, PO Box 9555, 6800 TA, Arnhem, The Netherlands b Department of Primary and Community Care, Radboud University Medical Centre, PO Box 9101, 6500 HB, Nijmegen, The Netherlands
c
Department of Clinical Research, Rijnstate Hospital, PO Box 9555, 6800 TA, Arnhem, The Netherlands d University of Twente, PO Box 217, 7500 AE, Enschede, The Netherlands e Department of Rheumatology and Clinical Immunology, Laboratory of Translational Immunology, Department of Immunology, University Medical Centre Utrecht, PO Box 85500, 3508 GA, Utrecht, The Netherlands f Scientific Institute for Quality of Healthcare, Radboud University Medical Centre, PO Box 9101, 6500 HB, Nijmegen, The Netherlands ∗ Corresponding
author. Tel.: +31 88 005 5400; fax: +31 88 005 6612. E-mail address: [email protected] (L.B.E. Kienhorst) Accepted 22 October 2014 Available online xxx
Please cite this article in press as: Kienhorst LBE, et al. The detection of monosodium urate crystals in synovial fluid after long-term and varying storage conditions. Joint Bone Spine (2015), http://dx.doi.org/10.1016/j.jbspin.2014.10.020
ARTICLE IN PRESS Joint Bone Spine xxx (2015) xxx–xxx
Available online at
ScienceDirect www.sciencedirect.com
Letter to the editor The detection of monosodium urate crystals in synovial fluid after long-term and varying storage conditions
a r t i c l e
i n f o
Keywords: Gout Monosodium urate crystals Diagnosis Synovial fluid storage
The gold standard for diagnosing gout is the identification of monosodium urate (MSU) crystals in synovial fluid by polarisation light microscopy (PLM) [1,2]. Most often, however, gout is diagnosed without this preferable gold standard, e.g. at emergency departments or in primary care, where PLM is not easily accessible. On contrary, PLM could be more widely used if knowledge would dictate that immediate analysis of synovial fluid is no necessity. To allow delayed assessment of MSU crystals the presence of such crystals should be stable to withstand sample storage and transportation [3,4]. The aim of this study was to determine the ability to detect MSU crystals after long-term storage at different temperatures. Synovial fluid aspirates of at least 1.2 mL (baseline) of 10 patients were collected at the rheumatology department of Rijnstate Hospital, The Netherlands, and were analyzed by experienced synovial fluid assessors (LK and MJ) for the presence of MSU crystals with PLM. Every aspirate with MSU crystals present at baseline was divided over 30 cuvets of at least 40 L each. Ten cuvets were stored at −20 ◦ C, 4 ◦ C and room temperature, respectively. No anticoagulant or preservative was added. All samples were re-analyzed by the same assessors for the presence of MSU crystals pseudo-randomly at several time-points until week 24. The Fig. 1 shows that detection of MSU crystals was still possible in the majority of synovial fluid samples, even after 24 weeks of storage. The total mean percentages of samples with re-identified MSU crystals present were 87, 69, and 89% in the −20 ◦ C, 4 ◦ C, and 20 ◦ C groups, respectively. The number of evaporated samples was the largest in the 20 ◦ C group. The presence of MSU crystals upon repetitive assessments over time was variable, which might be due to intra- and interobserver variability, and difference in the concentration of MSU crystals per sample. Our results are partially in accordance with the literature. In a systematic review of Graf et al., 5 studies [3–7] were analyzed concerning storage in synovial fluid of gout patients [8]. MSU crystals remained stable in synovial fluid stored at room temperature for 24–72 hours [4,5,9]. After this time period, the amount of MSU crystals decreased. Storage at 4 ◦ C slowed this process, and after 8 weeks in all patients MSU crystals could be identified [4]. We did
Fig. 1. The presence of MSU crystals in stored synovial fluid samples at three different temperatures. 5 samples of knee joints and 5 samples of ankle joints were included. In patient 7, MSU crystals were re-identified in every sample. Although in patients 4 and 5 MSU crystals were often not re-identified, they were re-assessed at every temperature at least once.
not study the amount of MSU crystals. However, our results did not show that more MSU crystals were re-identified after storage at 4 ◦ C compared to storage at 20 ◦ C. Our results agree with the literature that anticoagulation was not required [3]. And we show that not only dried cytospin preparations allowed long-term storage and delayed analysis [7], but also synovial fluid stored without any specific conservation process. Altogether, this study underscores that synovial aspirates can be stored for delayed analysis with PLM to detect MSU crystals. This could increase the availability of synovial fluid analysis to improve the validity of the diagnosis of gout at emergency departments and in primary care, when the facilities are not easily accessible. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. References [1] Wallace SL, Robinson H, Masi AT, et al. Preliminary criteria for the classification of the acute arthritis of primary gout. Arthritis Rheum 1977;20:895–900. [2] Zhang W, Doherty M, Pascual E, et al. EULAR evidence based recommendations for gout. Part I: diagnosis. Report of a task force of the Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis 2006;65:1301–11. [3] Galvez J, Saiz E, Linares LF, et al. Delayed examination of synovial fluid by ordinary and polarised light microscopy to detect and identify crystals. Ann Rheum Dis 2002;61:444–7. [4] Kerolus G, Clayburne G, Schumacher Jr HR. Is it mandatory to examine synovial fluids promptly after arthrocentesis? Arthritis Rheum 1989;32:271–8. [5] Bible MW, Pinals RS. Late precipitation of monosodium urate crystals. J Rheumatol 1982;9:480. [6] de Medicis R, Dansereau JY, Menard HA, et al. [Diagnosis of gout: problems caused by crystallization “in vitro” of sodium urate]. Union Med Can 1979;108:810 [2, 4 passim].
http://dx.doi.org/10.1016/j.jbspin.2014.10.020 1297-319X/© 2015 Published by Elsevier Masson SAS on behalf of the Société Française de Rhumatologie.
Please cite this article in press as: Kienhorst LBE, et al. The detection of monosodium urate crystals in synovial fluid after long-term and varying storage conditions. Joint Bone Spine (2015), http://dx.doi.org/10.1016/j.jbspin.2014.10.020
G Model BONSOI-4152; No. of Pages 2 2
ARTICLE IN PRESS Letter to the editor / Joint Bone Spine xxx (2015) xxx–xxx
[7] Robier C, Neubauer M, Stettin M, et al. Dried cytospin preparations of synovial fluid are a stable material for long-time storage and delayed crystal analysis. Clin Rheumatol 2012;31:1115–6. [8] Graf SW, Buchbinder R, Zochling J, et al. The accuracy of methods for urate crystal detection in synovial fluid and the effect of sample handling: a systematic review. Clin Rheumatol 2013;32:225–32. [9] Tausche AK, Gehrisch S, Panzner I, et al. A 3-day delay in synovial fluid crystal identification did not hinder the reliable detection of monosodium urate and calcium pyrophosphate crystals. J Clin Rheumatol 2013;19: 241–5.
Laura B.E. Kienhorst a,∗ Hein J.E.M. Janssens b,c Roelant S. Eijgelaar d Tim R.D.J. Radstake e Piet L.C.M. van Riel f Matthijs Janssen a a Department of Rheumatology, Rijnstate Hospital, PO Box 9555, 6800 TA, Arnhem, The Netherlands b Department of Primary and Community Care, Radboud University Medical Centre, PO Box 9101, 6500 HB, Nijmegen, The Netherlands
c
Department of Clinical Research, Rijnstate Hospital, PO Box 9555, 6800 TA, Arnhem, The Netherlands d University of Twente, PO Box 217, 7500 AE, Enschede, The Netherlands e Department of Rheumatology and Clinical Immunology, Laboratory of Translational Immunology, Department of Immunology, University Medical Centre Utrecht, PO Box 85500, 3508 GA, Utrecht, The Netherlands f Scientific Institute for Quality of Healthcare, Radboud University Medical Centre, PO Box 9101, 6500 HB, Nijmegen, The Netherlands ∗ Corresponding
author. Tel.: +31 88 005 5400; fax: +31 88 005 6612. E-mail address: [email protected] (L.B.E. Kienhorst) Accepted 22 October 2014 Available online xxx
Please cite this article in press as: Kienhorst LBE, et al. The detection of monosodium urate crystals in synovial fluid after long-term and varying storage conditions. Joint Bone Spine (2015), http://dx.doi.org/10.1016/j.jbspin.2014.10.020
