International Journal of Rheumatic Diseases 2015; 18: 352–359
ORIGINAL ARTICLE
Serum procalcitonin as a diagnostic aid in patients with acute bacterial septic arthritis Suangkanok PAOSONG, Pongthorn NARONGROEKNAWIN, Rattapol PAKCHOTANON, Paijit ASAVATANABODEE and Sumapa CHAIAMNUAY Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand
Abstract Introduction: Septic arthritis is a common and serious problem. Early detection and prompt treatment improve outcomes. Objective: To evaluate serum procalcitonin for diagnosis of acute bacterial septic arthritis and to compare its diagnostic utility with synovial white blood cells (WBC), erythrocyte sedimentation rate (ESR) and high-sensitivity C-reactive protein (hs-CRP). Method: A prospective cross-sectional study was performed in 78 Thai patients with acute arthritis. Patients with concomitant infections were excluded. Twenty-eight patients were diagnosed with acute bacterial septic arthritis and 50 patients were diagnosed with acute inflammatory arthritis. Blood samples were collected for complete blood count, ESR, hs-CRP, procalcitonin and hemoculture. Synovial fluid was sent for cell count, Gram stain, crystals identification and culture. The diagnostic accuracy by area under receiver operating characteristic (ROC) curve was calculated. Result: Patients with acute bacterial septic arthritis had higher procalcitonin levels than in acute inflammatory arthritis (mean SD = 1.48 2.30 vs. 0.44 0.92 ng/mL, P = 0.032). The cut-off level of procalcitonin was 0.5 ng/mL for which sensitivity, specificity and accuracy for diagnosis of bacterial septic arthritis were 59.3%, 86% and 75.3%, respectively. The ROC curve analysis showed that procalcitonin had a good diagnostic performance (area under the curve = 0.78, 95% CI 0.69–0.89). The area under the curve of hs-CRP and synovial fluid WBC were 0.67 (95% CI 0.55–0.79) and 0.821 (95% CI 0.720–0.923), respectively. Combining procalcitonin with other markers did not provide better sensitivity or specificity than procalcitonin alone. Conclusion: Serum procalcitonin has a potential role in diagnosing acute bacterial septic arthritis, especially if arthrocenthesis cannot be performed. Key words: diagnosis, high-sensitivity C-reactive protein, procalcitonin, septic arthritis.
INTRODUCTION Acute bacterial septic arthritis is a common serious problem in medical centers with an annual incidence of 0.002–0.01%.1 This condition is a medical emergency
Correspondence: Sumapa Chaiamnuay, Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand. Email: [email protected]
that may be associated with significant mortality, morbidity and irreversible loss of joint function in 10–15%, 25–50%, and up to 50% of patients, respectively.1 The consequences of delay in diagnosis and treatment are severe joint destruction, limited joint range of motion and deformities. Early differentiation between acute bacterial septic and non-septic arthritis can be difficult and might affect the treatment decision. The traditional signs for infections such as fever, constitutional symptoms, warmth,
© 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd
Procalcitonin for acute septic arthritis
redness and swelling of the joints can also be found among other causes of acute inflammatory non-septic arthritis, such as crystal-induced arthritis. Synovial fluid Gram stain yields only 50–60% in acute bacterial septic arthritis.1 Synovial fluid cultures have a higher yield in diagnosis of acute bacterial septic arthritis; however, the results take 3–5 days, which might delay the initiation of antibiotics. Procalcitonin is a protein that is encoded by the CALC-I gene on chromosome 11. Its concentration in serum of healthy subjects are undetectable or low, generally < 0.1 ng/mL.2 Inflammation and infectious injury stimulate the increase in serum procalcitonin. Serum procalcitonin is elevated in bacterial infections, but not in viral infections.3,4 Procalcitonin can be increased during severe bacterial infection, sepsis, septic shock and multiple organ failure.3,5 In contrast, procalcitonin was reported to have suboptimal diagnostic performance in localized infections.4,5 Previous studies observed that noninfectious triggers, such as surgical trauma, Kawasaki disease and adult-onset Still’s disease can induce procalcitonin elevation.4 This study aimed to examine the clinical utility of serum procalcitonin for early differentiation of acute bacterial septic arthritis and acute inflammatory nonseptic arthritis in addition to clinical signs and symptoms.
MATERIALS AND METHODS The protocol for the research project was approved by a suitably constituted Ethics Committee of the institution within which the work was undertaken and it conforms to the provisions of the World Medical Association’s Declaration of Helsinki. Informed consent was obtained before conducting the study.
Study design
3 no organism isolated but a histological or radiological evidence of infection; b turbid fluid aspirated from joint. Patients were excluded from the study if: (i) they had a major operation, burn, previous antibiotics taken within 5 days; (ii) patients had multiple organ failure, thyroid cancer or bone fractures; (iii) patients had both acute bacterial septic arthritis and acute inflammatory non-septic arthritis; and (iv) patients had other concomitant infections.
Clinical evaluation Baseline patient characteristics were collected, including age, sex, body mass index (BMI), fever, chill, underlying disease, history of previous antibiotics use, history of prosthesis, history of intravenous drug use (IVDU), previous use of immunosuppressive drugs, history of intraarticular steroid injection, current smoking, current alcohol consumption, history of herbal medication, onset of arthritis and number of arthritis joints were recorded. All patients were examined by physicians. Body temperature, pain score by visual analog scale (VAS 0–10 cm), number of joints involved and the presence of tophi were recorded. Sepsis was defined as having systemic inflammatory response syndrome (SIRS). SIRS can be diagnosed when two or more of the following criteria are present:7 1 body temperature less than 36°C or greater than 38°C; 2 heart rate greater than 90 beats/min; 3 respiratory rate greater than 20 breaths/min or an arterial partial pressure of carbon dioxide less than 4.3 kPa (32 mmHg); and 4 leukocytes less than 4000 cells/lL³ or greater than 12 000 cells/lL or the presence of greater than 10% immature neutrophils (band forms).
This was a prospective cross-sectional study.
Study population Seventy-eight patients were enrolled from Phramongkutklao Hospital, Bangkok, Thailand between 1 March 2012 and 1 January 2013. All patients were over 18 years old and must have had arthritis in at least one joint with the duration of arthritis less than 14 days. Septic arthritis was diagnosed according to the Newman criteria diagnosis6 for septic arthritis which met one of the following criteria: 1 organism isolated from joint; 2 organism isolated from elsewhere; and
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Laboratory measurements Basic laboratory Complete blood count (CBC), urine analysis (UA) and hemoculture were performed. Arthrocentesis was performed in all patients, and synovial fluids were sent for synovial cell count, culture and crystals identification. Crystals were identified using polarized light microscopy. Biological marker Serum procalcitonin, high-sensitivity C-reactive protein (hs-CRP) and erythrocyte sedimentation rate (ESR)
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were collected in all patients. The hs-CRP was measured by particle-enhanced immunoturbidimetric assay (Roche Diagnostics GmbH, Mannheim, Germany). Assay of procalcitonin Serum procalcitonin concentration was measured using the electrochemiluminescence immunoassay (ECLIA) method (Roche Diagnostics GmbH) with a detection limit of 0.02 ng/mL.
Statistical analysis Continuous variables were expressed as mean SD. Categorical variables were compared using the Chisquare test. The continuous variables were compared with Student’s t-test if the variables were normally distributed or the Mann–Whitney test if the variables were not normally distributed. The Shapiro–Wilk test was used to assess whether data were likely from a normal distribution. All P-values were two-tailed. The level of statistical significance was defined as P < 0.01. The diagnostic performance of serum procalcitonin level, hs-CRP, ESR and synovial fluid white blood cell count (WBC), as well as the cut-off of serum procalcitonin for early diagnosis of acute bacterial septic arthritis were examined by the area under the corresponding receiver operating characteristic (ROC) curve analysis. The sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy were further examined by a constructed 2 9 2 table. The P-value < 0.05 was considered as statistically significant for all analyses.
RESULT Patients demographic and laboratory data Seventy-eight patients were included in this study. Twenty-eight patients had acute bacterial septic arthritis and 50 patients had acute inflammatory non-septic arthritis. The common pathogens in the septic arthritis group were Staphylococcus aureus and Streptococcus group B. The other pathogens were Streptococcus bovis, Streptococcus viridians, Campylobacter fetus and Neisseria gonorrhea. In six cases the organisms were not identified; however, they met the Newman diagnostic criteria for septic arthritis since they had purulent synovial fluid. Furthermore, these patients also had rapid radiographic progression consistent with septic arthritis and responded well to antibiotic treatment. In the acute inflammatory non-septic arthritis group, patients had gout, pseudogout, a flare of ankylosing spondylitis, reactive arthritis and a flare of rheumatoid arthritis. The
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diagnosis of conditions in patients in our study are presented in Table 1. Patients with acute bacterial septic arthritis were younger than patients with acute bacterial non-septic arthritis (mean SD = 56.96 17.01 vs. 66.42 16.7, P = 0.02). The former also had higher body temperature, greater history of chills and more sepsis syndrome than the latter (mean SD = 38.27 0.74 vs. 37.21 0.69°C, P < 0.001 and n, % = 5, 10% vs. 14, 50%, P < 0.001 and 1, 2% vs. 11, 39%, P < 0.001, respectively). Tophi were only found in the non-septic group. However, no differences were observed in sex, number of joints involved or disease duration between the two groups. The baseline demographic data and other comorbidities of patients with acute bacterial septic arthritis and acute inflammatory non-septic arthritis are presented in Table 2. Patients with acute bacterial septic arthritis had higher synovial fluid WBC, serum WBC and higher serum polymorphonuclear cell percentages than patients with acute inflammatory non-septic arthritis (mean SD = 48 226 23 875 vs. 21 064 17 524 cells/mm3, P < 0.001, 16 182 7 336 vs. 10 060 3766 cells/mm3, P < 0.001 and 81 8 vs. 68 14, P < 0.001, respectively). The laboratory data are shown in Table 2.
Serum procalcitonin, hs-CRP and ESR measurements Serum procalcitonin was significantly higher in the acute bacterial septic arthritis group than acute
Table 1 The diagnoses of patients in the study Diagnosis
N
Bacterial septic arthritis Streptococcus group B Staphylococcus aureus Streptococcus bovis Streptococcus viridians Campylobacter fetus Neisseria gonorrhea No growth culture Crystal induced arthritis Gout Pseudogout Both gout and pseudogout Ankylosing spondylitis Reactive arthritis Rheumatoid arthritis Total
28 11 7 1 1 1 1 6 24 14 1 1 4 6 78
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Table 2 Demographic, other co-morbidities and laboratory data of patients with acute bacterial septic arthritis and acute inflammatory septic arthritis Variables Age (years, mean SD) Body temperature (Celsius, mean SD) History of chills (n, %) Number of joint involvement (n, mean SD) Pain VAS* (mean SD) Disease duration (day, mean SD) BMI (kg/m2, mean SD) Sepsis syndrome (n, %) Tophi (n, %) Diabetes mellitus (n, %) Chronic kidney disease (n, %) Cirrhosis (n, %) Procalcitonin (ng/mL) Mean SD Median (IQR† 25-IQR75) hs-CRP (mg/L) Mean SD Median (IQR25-IQR75) ESR (mm/h) Mean SD Median (IQR25-IQR75) Synovial fluid WBC (cell/mm3) Mean SD Median (IQR25-IQR75) Serum white blood cell count (cells/mm3, mean SD) Serum neutrophil (%, mean SD)
Acute inflammatory non-septic arthritis (n = 50)
Acute bacterial septic arthritis (n = 28)
P-value
66.4 16.7 37.2 0.7 5, 10% 2.6 3.5 6.8 1.8 6.2 3.9 24.4 4.1 1, 2% 7, 14% 11, 22% 8, 16% 0%
57.0 17.0 38.3 0.7 14, 50% 2.2 1.3 7.2 2.1 7.0 5.5 23.4 5.1 11, 39% 0% 5, 18% 1, 4% 3, 11%
0.020 < 0.001 < 0.001 0.489 0.394 0.542 0.353 < 0.001 0.045 0.775 0.146 0.043
0.44 0.92 0.11 (0.07–0.40)
1.48 2.30 0.78 (0.27–1.32)
0.032 < 0.001
119.94 94.08 100.57 (40–201.17) 89.40 35.28 99.00 (64.00–116.00) 21 064 17 524 17 240 (7200–29 600) 10 060 3767 68.72 14.36
171.76 83.79 168.24 (106.00–246.50)
0.018 0.012
102.18 31.10 111.50 (93.50–121.00)
0.114 0.100
48 226 23 875 45 730 (32 960–68 000) 16 182 7336 81.32 8.37
< 0.001 < 0.001 < 0.001 < 0.001
*Visual Analog Scale. †Interquartile range.
inflammatory non-septic arthritis group (mean SD = 1.48 2.30 vs. 0.44 0.92 ng/mL, P = 0.032) as well as the hs-CRP (mean SD = 174 84 vs. 120 94 mg/L, P = 0.018). The box plots are shown in Fig. 1. The performances of procalcitonin, hs-CRP, synovial fluid WBC and ESR as a diagnostic tool for acute bacterial septic arthritis patients were assessed through the area under the ROC curve. Procalcitonin and hs-CRP performed well in differentiating acute bacterial septic arthritis and acute inflammatory nonseptic arthritis. The area under the ROC curve of procalcitonin and hs-CRP in diagnosis of acute bacterial septic arthritis were 0.798 (95% CI 0.686–0.891) and 0.672 (95% CI 0.553–0.791), respectively. ESR was not a good parameter for diagnosing acute bacterial septic arthritis; the ROC was 0.613 (95% CI 0.483– 0.743). The synovial fluid WBC had the highest diagnostic performance (the area under the ROC curve
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0.821, 95% CI 0.720–0. 923). These results are shown in Table 3 and Fig. 2. The cut-off level of procalcitonin used to differentiate acute bacterial septic arthritis and acute inflammatory non-septic arthritis from previous studies was 0.5 ng/mL.8,9 The cut-off of 0.5 ng/mL in this study provided the sensitivity of 59%, specificity of 84%, positive predictive value of 66.7%, negative predictive value of 79.2% and overall accuracy of 75.3%. However, from the ROC curve, the cut-off level of 0.66 ng/mL had slightly higher overall accuracy (sensitivity of 59%, specificity of 86%, positive predictive value of 69.6%, negative predictive value of 79.6% and overall accuracy of 77%) than the cut-off level of 0.5 ng/mL. Serum procalcitonin level was correlated with the degree of fever, serum WBC, synovial fluid WBC and hs-CRP but not ESR. The correlations between these parameters are shown in Table 4.
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(a)
(b)
(c)
(d)
Figure 1 Box-plot of procalcitonin (a), high sensitivity C-reactive protein, hs-CRP (b), erythrocyte sedimentation rate, ESR (c) and synovial white blood cell count (d) in pateints with acute bacterial septic arthritis and acute non-inflammatory septic arthritis.
Table 3 Area under the curve of procalcitonin, hs-CRP, ESR and synovial fluid white blood cell count for diagnosis acute bacterial septic arthritis Variable(s) Procalcitonin Hs-CRP ESR Synovial white blood cell count
Area under the curve
95% Confidence interval
0.789 0.672 0.613 0.821
0.686–0.891 0.553–0.791 0.483–0.743 0.720–0.923
DISCUSSION Our study demonstrated that serum procalcitonin could be a potential marker for early distinction between septic and non-septic arthritis. Our study revealed similar results with previous studies8–10 in that serum procalcitonin levels were significantly higher in patients with acute bacterial septic arthritis than in patients with acute inflammatory nonseptic arthritis. However, few studies have reported that serum procalcitonin levels did not differ between patients with septic and nonseptic arthritis.11,12 Table 5 summarizes previous studies investigating the diagnostic utility of procalcitonin in acute bacterial septic arthritis. The cut-off level used for the diagnosis of septic arthritis remains uncertain. The cut-off used in our study was 0.5 ng/mL, which was used in most studies; nevertheless, the level of 0.66 ng/mL had slightly
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Figure 2 The ROC curve analysis of procalcitonin, hs-CRP and ESR for the diagnosis of acute bacterial septic arthritis.
higher specificity (86%) than the 0.5 ng/mL level (84%) with similar sensitivity (59%). Recently, metaanalysis of the diagnostic performance of serum procalcitonin in the identification of osteomyelitis and septic arthritis was investigated in patients who presented with fever and orthopedic symptoms. It was reported that the lower cut-off value of 0.2-0.3 ng/mL improved the sensitivity to 90% but had no significant
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Table 4 Correlation Coefficient of procalcitonin and other laboratory measurement Procalcitonin (ng/mL)
ESR (mm/h)
Synovial white blood cell (cell/mm3)
Serum white blood cell (cell/mm3)
Fever (°C)
1.000 –
0.451* 0.000
0.246† 0.030
0.323* 0.004
0.230† 0.045
0.451* 0.001
1.000 –
0.140 0.221
0.057 0.620
0.064 0.583
0.246† 0.030
0.140 0.221
1.000 –
0.366* 0.001
0.309* 0.006
0.323* 0.004
0.057 0.620
0.366* 0.001
1.000 –
0.140 0.223
0.230† 0.045
0.064 0.583
0.309* 0.006
0.140 0.223
1.000 –
Hs-CRP (mg/L)
Hs-CRP(mg/L) Rho 0.368* P-value 0.001 ESR (mm/h) Rho 0.157 P-value 0.174 < Synovial white blood cell (cell/mm3) Rho 0.422* P-value < 0.001 Serum white blood cell (cell/mm3) Rho 0.334* P-value 0.003 Fever (°C) Rho 0.395* P-value < 0.001
*Correlation is significant at the 0.01 level (2-tailed). †Correlation is significant at the 0.05 level (2-tailed).
Table 5 Procalcitonin levels, sensitivity and specificity in previous studies Author Butbul-Aviel Y21 Faesch et al22 Hugle et al8 Talebi-Taher et al.10 Martinot et al14 Fottner et al9 This study
Population
Number of patients
Procalcitonin (ng/mL)
Sensitivity (%)
Specificity (%)
Septic arthritis, osteomyelitis Septic arthritis, osteomyelitis Septic/non septic arthritis Septic/non septic arthritis Septic/non septic arthritis Septic/non septic arthritis Septic/non septic arthritis
42 42 42 75 42 33 78
0.5 0.5 0.25 0.5 0.5 0.5 0.5
44 25 93 68 55 53 59
100 97 93 80 94 100 84
effect on specificity (87%) and suggested that the lower cut-off should be used for localized infection such as septic arthritis.13 However, in our study a cut-off of 0.25 ng/mL provided a higher sensitivity of 78% but lower specificity of 64% with a lower overall diagnostic accuracy of 69% than a cut-off of 0.5 ng/mL. Three studies examined the role of synovial fluid procalcitonin in the diagnosis of acute bacterial septic arthritis. They found that patients with septic arthritis had significantly higher synovial fluid procalcitonin than patients with non-septic arthritis, such as rheumatoid arthritis, osteoarthritis and crystal-induced arthritis. However, serum procalcitonin performed better than synovial fluid procalcitonin in the diagnosis of septic arthritis,10,14,15 We also examined other parameters, such as hs-CRP, ESR and synovial fluid WBC, which could be helpful in diagnosing septic arthritis. Similar to previous reports,10
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we found that synovial fluid WBC performed the best and slightly better than serum procalcitonin in diagnosing septic arthritis. Thus, in patients with suspected acute bacterial septic arthritis where arthrocentesis could not be performed or in patients whose synovial fluid WBC was unreliable, such as patients given antibiotics before arthrocentesis and patients with leukopenia, serum procalcitonin could be a helpful diagnostic aid. However, if patients had concomitant infection elsewhere, for example, thyroid cancer, post-major operation and septic shock patients, serum procalcitonin could also be elevated16 and these limit the use of serum procalcitonin as a biomarker for acute bacterial septic arthritis. Our study along with previous reports demonstrated that hs-CRP is elevated in patients with septic arthritis; however, serum procalcitonin performed better in diagnosing acute bacterial septic arthritis.4,10,14 In contrast
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to other parameters, ESR did not differ between patients with and without septic arthritis and should not be used as a diagnostic tool to diagnose septic arthritis. Procalcitonin was reported to be useful in diagnosing blood stream infection, septic shock, bacteremia, community-acquired pneumonia and hospital-acquired pneumonia.2,17–19 Antibiotics treatment is strongly encouraged in communities that acquire pneumonia if procalcitonin level is greater than 0.5 ng/mL.20 Procalcitonin could be a potential useful biomarker to diagnose acute bacterial septic arthritis. The level of procalcitonin can be obtained promptly and thus, it could be used along with other clinical information to differentiate between acute bacterial septic arthritis and acute inflammatory non-septic arthritis before the result of synovial culture can be obtained. However, the costeffectiveness of using procalcitonin as a diagnostic aid for acute bacterial septic arthritis was not examined and would be interesting for future research. This study had some limitations. First, the level of serum procalcitonin decreased after the onset of bacteremia. However, in our study patients in both groups presented quite late (mean SD 6.2 3.9 days and 7.0 5.5 days for acute bacterial septic arthritis and inflammatory non-septic arthritis, respectively). Thus, serum procalcitonin was measured several days after onset of arthritis. Second, our study used Newman’s criteria to diagnose septic arthritis and synovial fluid cultures of six patients that were negative. Thus, it can be argued that these six patients really had septic arthritis.
CONCLUSION Serum procalcitonin may have a potential role in differentiating acute bacterial septic arthritis from acute inflammatory non-septic arthritis, especially in patients for whom arthrocentesis cannot be performed. It has a good diagnostic predictability for acute bacterial septic arthritis and is modestly correlated with fever, hs-CRP, serum and synovial fluid WBC.
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DISCLOSURES All authors have no conflicts of interest pertaining to this article.
REFERENCES 1 Marker-Hermann E (2008) Septic arthritis, osteomyelitis, gonococcal and syphilitic arthritis. In: Hochberg MC,
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Silman AJ, Smolen JS, Weinblatt ME, Weisman ME, eds. Rheumatology. Vol 2. 4th edn, pp 1013–28. Elsevier Limited, Spain. Seligman R, Ramos-Lima LF, Oliveira VA, Sanvicente C, Pacheco EF, Dalla Rosa K (2012) Biomarkers in community-acquired pneumonia: a state-of-the-art review. Clinics (Sao Paulo) 67, 1321–5. Muller B, Becker KL, Schachinger H et al. (2000) Calcitonin precursors are reliable markers of sepsis in a medical intensive care unit. Crit Care Med 28, 977–83. Becker KL, Snider R, Nylen ES (2010) Procalcitonin in sepsis and systemic inflammation: a harmful biomarker and a therapeutic target. Br J Pharmacol 159, 253–64. Becker KL, Nylen ES, White JC, Muller B, Snider RH Jr (2004) Clinical review 167: procalcitonin and the calcitonin gene family of peptides in inflammation, infection, and sepsis: a journey from calcitonin back to its precursors. J Clin Endocrinol Metab 89, 1512–25. Newman JH (1976) Review of septic arthritis throughout the antibiotic era. Ann Rheum Dis 35, 198–205. American College of Chest Physicians/Society of Critical Care (1992) Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 20, 864–74. Hugle T, Schuetz P, Mueller B et al. (2008) Serum procalcitonin for discrimination between septic and non-septic arthritis. Clin Exp Rheumatol 26, 453–6. Fottner A, Birkenmaier C, von Schulze Pellengahr C, Wegener B, Jansson V (2008) Can serum procalcitonin help to differentiate between septic and nonseptic arthritis? Arthroscopy 24 229–33. Talebi-Taher M, Shirani F, Nikanjam N, Shekarabi M (2013) Septic versus inflammatory arthritis: discriminating the ability of serum inflammatory markers. Rheumatol Int 33, 319–24. Lorrot M, Fitoussi F, Faye A et al. (2007) Laboratory studies in pediatric bone and joint infections. Arch Pediatr 14 (Suppl 2), S86–90. Soderquist B, Jones I, Fredlund H, Vikerfors T (1998) Bacterial or crystal-associated arthritis? Discriminating ability of serum inflammatory markers. Scand J Infect Dis 30, 591–6. Shen CJ, Wu MS, Lin KH et al. (2013) The use of procalcitonin in the diagnosis of bone and joint infection: a systemic review and meta-analysis. Eur J Clin Microbiol Infect Dis 32, 807–14. Martinot M, Sordet C, Soubrier M et al. (2005) Diagnostic value of serum and synovial procalcitonin in acute arthritis: a prospective study of 42 patients. Clin Exp Rheumatol 23, 303–10. Streit G, Alber D, Toubin MM, Toussirot E, Wendling D (2008) Procalcitonin, C-reactive protein, and complement-3a assays in synovial fluid for diagnosing septic arthritis: preliminary results. Joint Bone Spine 75, 238–9.
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16 Muller B, Christ-Crain M, Nylen ES, Snider R, Becker KL (2004) Limits to the use of the procalcitonin level as a diagnostic marker. Clin Infect Dis 39, 1867–8. 17 Kibe S, Adams K, Barlow G (2011) Diagnostic and prognostic biomarkers of sepsis in critical care. J Antimicrob Chemother 66(Suppl 2), ii33–40. 18 Polzin A, Pletz M, Erbes R et al. (2003) Procalcitonin as a diagnostic tool in lower respiratory tract infections and tuberculosis. Eur Respir J 21, 939–43. 19 Boussekey N, Leroy O, Georges H, Devos P, d’Escrivan T, Guery B (2005) Diagnostic and prognostic values of admission procalcitonin levels in community-acquired pneumonia in an intensive care unit. Infection 33, 257–63.
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20 Christ-Crain M, Stolz D, Bingisser R et al. (2006) Procalcitonin guidance of antibiotic therapy in communityacquired pneumonia: a randomized trial. Am J Respir Crit Care Med 174 (1), 84–93. 21 Butbul-Aviel Y, Koren A, Halevy R, Sakran W (2005) Procalcitonin as a diagnostic aid in osteomyelitis and septic arthritis. Pediatr Emerg Care 21, 828–32. 22 Faesch S, Cojocaru B, Hennequin C et al. (2009) Can procalcitonin measurement help the diagnosis of osteomyelitis and septic arthritis? A prospective trial. Ital J Pediatr 35 (1), 33.
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ORIGINAL ARTICLE
Serum procalcitonin as a diagnostic aid in patients with acute bacterial septic arthritis Suangkanok PAOSONG, Pongthorn NARONGROEKNAWIN, Rattapol PAKCHOTANON, Paijit ASAVATANABODEE and Sumapa CHAIAMNUAY Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand
Abstract Introduction: Septic arthritis is a common and serious problem. Early detection and prompt treatment improve outcomes. Objective: To evaluate serum procalcitonin for diagnosis of acute bacterial septic arthritis and to compare its diagnostic utility with synovial white blood cells (WBC), erythrocyte sedimentation rate (ESR) and high-sensitivity C-reactive protein (hs-CRP). Method: A prospective cross-sectional study was performed in 78 Thai patients with acute arthritis. Patients with concomitant infections were excluded. Twenty-eight patients were diagnosed with acute bacterial septic arthritis and 50 patients were diagnosed with acute inflammatory arthritis. Blood samples were collected for complete blood count, ESR, hs-CRP, procalcitonin and hemoculture. Synovial fluid was sent for cell count, Gram stain, crystals identification and culture. The diagnostic accuracy by area under receiver operating characteristic (ROC) curve was calculated. Result: Patients with acute bacterial septic arthritis had higher procalcitonin levels than in acute inflammatory arthritis (mean SD = 1.48 2.30 vs. 0.44 0.92 ng/mL, P = 0.032). The cut-off level of procalcitonin was 0.5 ng/mL for which sensitivity, specificity and accuracy for diagnosis of bacterial septic arthritis were 59.3%, 86% and 75.3%, respectively. The ROC curve analysis showed that procalcitonin had a good diagnostic performance (area under the curve = 0.78, 95% CI 0.69–0.89). The area under the curve of hs-CRP and synovial fluid WBC were 0.67 (95% CI 0.55–0.79) and 0.821 (95% CI 0.720–0.923), respectively. Combining procalcitonin with other markers did not provide better sensitivity or specificity than procalcitonin alone. Conclusion: Serum procalcitonin has a potential role in diagnosing acute bacterial septic arthritis, especially if arthrocenthesis cannot be performed. Key words: diagnosis, high-sensitivity C-reactive protein, procalcitonin, septic arthritis.
INTRODUCTION Acute bacterial septic arthritis is a common serious problem in medical centers with an annual incidence of 0.002–0.01%.1 This condition is a medical emergency
Correspondence: Sumapa Chaiamnuay, Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand. Email: [email protected]
that may be associated with significant mortality, morbidity and irreversible loss of joint function in 10–15%, 25–50%, and up to 50% of patients, respectively.1 The consequences of delay in diagnosis and treatment are severe joint destruction, limited joint range of motion and deformities. Early differentiation between acute bacterial septic and non-septic arthritis can be difficult and might affect the treatment decision. The traditional signs for infections such as fever, constitutional symptoms, warmth,
© 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd
Procalcitonin for acute septic arthritis
redness and swelling of the joints can also be found among other causes of acute inflammatory non-septic arthritis, such as crystal-induced arthritis. Synovial fluid Gram stain yields only 50–60% in acute bacterial septic arthritis.1 Synovial fluid cultures have a higher yield in diagnosis of acute bacterial septic arthritis; however, the results take 3–5 days, which might delay the initiation of antibiotics. Procalcitonin is a protein that is encoded by the CALC-I gene on chromosome 11. Its concentration in serum of healthy subjects are undetectable or low, generally < 0.1 ng/mL.2 Inflammation and infectious injury stimulate the increase in serum procalcitonin. Serum procalcitonin is elevated in bacterial infections, but not in viral infections.3,4 Procalcitonin can be increased during severe bacterial infection, sepsis, septic shock and multiple organ failure.3,5 In contrast, procalcitonin was reported to have suboptimal diagnostic performance in localized infections.4,5 Previous studies observed that noninfectious triggers, such as surgical trauma, Kawasaki disease and adult-onset Still’s disease can induce procalcitonin elevation.4 This study aimed to examine the clinical utility of serum procalcitonin for early differentiation of acute bacterial septic arthritis and acute inflammatory nonseptic arthritis in addition to clinical signs and symptoms.
MATERIALS AND METHODS The protocol for the research project was approved by a suitably constituted Ethics Committee of the institution within which the work was undertaken and it conforms to the provisions of the World Medical Association’s Declaration of Helsinki. Informed consent was obtained before conducting the study.
Study design
3 no organism isolated but a histological or radiological evidence of infection; b turbid fluid aspirated from joint. Patients were excluded from the study if: (i) they had a major operation, burn, previous antibiotics taken within 5 days; (ii) patients had multiple organ failure, thyroid cancer or bone fractures; (iii) patients had both acute bacterial septic arthritis and acute inflammatory non-septic arthritis; and (iv) patients had other concomitant infections.
Clinical evaluation Baseline patient characteristics were collected, including age, sex, body mass index (BMI), fever, chill, underlying disease, history of previous antibiotics use, history of prosthesis, history of intravenous drug use (IVDU), previous use of immunosuppressive drugs, history of intraarticular steroid injection, current smoking, current alcohol consumption, history of herbal medication, onset of arthritis and number of arthritis joints were recorded. All patients were examined by physicians. Body temperature, pain score by visual analog scale (VAS 0–10 cm), number of joints involved and the presence of tophi were recorded. Sepsis was defined as having systemic inflammatory response syndrome (SIRS). SIRS can be diagnosed when two or more of the following criteria are present:7 1 body temperature less than 36°C or greater than 38°C; 2 heart rate greater than 90 beats/min; 3 respiratory rate greater than 20 breaths/min or an arterial partial pressure of carbon dioxide less than 4.3 kPa (32 mmHg); and 4 leukocytes less than 4000 cells/lL³ or greater than 12 000 cells/lL or the presence of greater than 10% immature neutrophils (band forms).
This was a prospective cross-sectional study.
Study population Seventy-eight patients were enrolled from Phramongkutklao Hospital, Bangkok, Thailand between 1 March 2012 and 1 January 2013. All patients were over 18 years old and must have had arthritis in at least one joint with the duration of arthritis less than 14 days. Septic arthritis was diagnosed according to the Newman criteria diagnosis6 for septic arthritis which met one of the following criteria: 1 organism isolated from joint; 2 organism isolated from elsewhere; and
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Laboratory measurements Basic laboratory Complete blood count (CBC), urine analysis (UA) and hemoculture were performed. Arthrocentesis was performed in all patients, and synovial fluids were sent for synovial cell count, culture and crystals identification. Crystals were identified using polarized light microscopy. Biological marker Serum procalcitonin, high-sensitivity C-reactive protein (hs-CRP) and erythrocyte sedimentation rate (ESR)
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were collected in all patients. The hs-CRP was measured by particle-enhanced immunoturbidimetric assay (Roche Diagnostics GmbH, Mannheim, Germany). Assay of procalcitonin Serum procalcitonin concentration was measured using the electrochemiluminescence immunoassay (ECLIA) method (Roche Diagnostics GmbH) with a detection limit of 0.02 ng/mL.
Statistical analysis Continuous variables were expressed as mean SD. Categorical variables were compared using the Chisquare test. The continuous variables were compared with Student’s t-test if the variables were normally distributed or the Mann–Whitney test if the variables were not normally distributed. The Shapiro–Wilk test was used to assess whether data were likely from a normal distribution. All P-values were two-tailed. The level of statistical significance was defined as P < 0.01. The diagnostic performance of serum procalcitonin level, hs-CRP, ESR and synovial fluid white blood cell count (WBC), as well as the cut-off of serum procalcitonin for early diagnosis of acute bacterial septic arthritis were examined by the area under the corresponding receiver operating characteristic (ROC) curve analysis. The sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy were further examined by a constructed 2 9 2 table. The P-value < 0.05 was considered as statistically significant for all analyses.
RESULT Patients demographic and laboratory data Seventy-eight patients were included in this study. Twenty-eight patients had acute bacterial septic arthritis and 50 patients had acute inflammatory non-septic arthritis. The common pathogens in the septic arthritis group were Staphylococcus aureus and Streptococcus group B. The other pathogens were Streptococcus bovis, Streptococcus viridians, Campylobacter fetus and Neisseria gonorrhea. In six cases the organisms were not identified; however, they met the Newman diagnostic criteria for septic arthritis since they had purulent synovial fluid. Furthermore, these patients also had rapid radiographic progression consistent with septic arthritis and responded well to antibiotic treatment. In the acute inflammatory non-septic arthritis group, patients had gout, pseudogout, a flare of ankylosing spondylitis, reactive arthritis and a flare of rheumatoid arthritis. The
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diagnosis of conditions in patients in our study are presented in Table 1. Patients with acute bacterial septic arthritis were younger than patients with acute bacterial non-septic arthritis (mean SD = 56.96 17.01 vs. 66.42 16.7, P = 0.02). The former also had higher body temperature, greater history of chills and more sepsis syndrome than the latter (mean SD = 38.27 0.74 vs. 37.21 0.69°C, P < 0.001 and n, % = 5, 10% vs. 14, 50%, P < 0.001 and 1, 2% vs. 11, 39%, P < 0.001, respectively). Tophi were only found in the non-septic group. However, no differences were observed in sex, number of joints involved or disease duration between the two groups. The baseline demographic data and other comorbidities of patients with acute bacterial septic arthritis and acute inflammatory non-septic arthritis are presented in Table 2. Patients with acute bacterial septic arthritis had higher synovial fluid WBC, serum WBC and higher serum polymorphonuclear cell percentages than patients with acute inflammatory non-septic arthritis (mean SD = 48 226 23 875 vs. 21 064 17 524 cells/mm3, P < 0.001, 16 182 7 336 vs. 10 060 3766 cells/mm3, P < 0.001 and 81 8 vs. 68 14, P < 0.001, respectively). The laboratory data are shown in Table 2.
Serum procalcitonin, hs-CRP and ESR measurements Serum procalcitonin was significantly higher in the acute bacterial septic arthritis group than acute
Table 1 The diagnoses of patients in the study Diagnosis
N
Bacterial septic arthritis Streptococcus group B Staphylococcus aureus Streptococcus bovis Streptococcus viridians Campylobacter fetus Neisseria gonorrhea No growth culture Crystal induced arthritis Gout Pseudogout Both gout and pseudogout Ankylosing spondylitis Reactive arthritis Rheumatoid arthritis Total
28 11 7 1 1 1 1 6 24 14 1 1 4 6 78
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Table 2 Demographic, other co-morbidities and laboratory data of patients with acute bacterial septic arthritis and acute inflammatory septic arthritis Variables Age (years, mean SD) Body temperature (Celsius, mean SD) History of chills (n, %) Number of joint involvement (n, mean SD) Pain VAS* (mean SD) Disease duration (day, mean SD) BMI (kg/m2, mean SD) Sepsis syndrome (n, %) Tophi (n, %) Diabetes mellitus (n, %) Chronic kidney disease (n, %) Cirrhosis (n, %) Procalcitonin (ng/mL) Mean SD Median (IQR† 25-IQR75) hs-CRP (mg/L) Mean SD Median (IQR25-IQR75) ESR (mm/h) Mean SD Median (IQR25-IQR75) Synovial fluid WBC (cell/mm3) Mean SD Median (IQR25-IQR75) Serum white blood cell count (cells/mm3, mean SD) Serum neutrophil (%, mean SD)
Acute inflammatory non-septic arthritis (n = 50)
Acute bacterial septic arthritis (n = 28)
P-value
66.4 16.7 37.2 0.7 5, 10% 2.6 3.5 6.8 1.8 6.2 3.9 24.4 4.1 1, 2% 7, 14% 11, 22% 8, 16% 0%
57.0 17.0 38.3 0.7 14, 50% 2.2 1.3 7.2 2.1 7.0 5.5 23.4 5.1 11, 39% 0% 5, 18% 1, 4% 3, 11%
0.020 < 0.001 < 0.001 0.489 0.394 0.542 0.353 < 0.001 0.045 0.775 0.146 0.043
0.44 0.92 0.11 (0.07–0.40)
1.48 2.30 0.78 (0.27–1.32)
0.032 < 0.001
119.94 94.08 100.57 (40–201.17) 89.40 35.28 99.00 (64.00–116.00) 21 064 17 524 17 240 (7200–29 600) 10 060 3767 68.72 14.36
171.76 83.79 168.24 (106.00–246.50)
0.018 0.012
102.18 31.10 111.50 (93.50–121.00)
0.114 0.100
48 226 23 875 45 730 (32 960–68 000) 16 182 7336 81.32 8.37
< 0.001 < 0.001 < 0.001 < 0.001
*Visual Analog Scale. †Interquartile range.
inflammatory non-septic arthritis group (mean SD = 1.48 2.30 vs. 0.44 0.92 ng/mL, P = 0.032) as well as the hs-CRP (mean SD = 174 84 vs. 120 94 mg/L, P = 0.018). The box plots are shown in Fig. 1. The performances of procalcitonin, hs-CRP, synovial fluid WBC and ESR as a diagnostic tool for acute bacterial septic arthritis patients were assessed through the area under the ROC curve. Procalcitonin and hs-CRP performed well in differentiating acute bacterial septic arthritis and acute inflammatory nonseptic arthritis. The area under the ROC curve of procalcitonin and hs-CRP in diagnosis of acute bacterial septic arthritis were 0.798 (95% CI 0.686–0.891) and 0.672 (95% CI 0.553–0.791), respectively. ESR was not a good parameter for diagnosing acute bacterial septic arthritis; the ROC was 0.613 (95% CI 0.483– 0.743). The synovial fluid WBC had the highest diagnostic performance (the area under the ROC curve
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0.821, 95% CI 0.720–0. 923). These results are shown in Table 3 and Fig. 2. The cut-off level of procalcitonin used to differentiate acute bacterial septic arthritis and acute inflammatory non-septic arthritis from previous studies was 0.5 ng/mL.8,9 The cut-off of 0.5 ng/mL in this study provided the sensitivity of 59%, specificity of 84%, positive predictive value of 66.7%, negative predictive value of 79.2% and overall accuracy of 75.3%. However, from the ROC curve, the cut-off level of 0.66 ng/mL had slightly higher overall accuracy (sensitivity of 59%, specificity of 86%, positive predictive value of 69.6%, negative predictive value of 79.6% and overall accuracy of 77%) than the cut-off level of 0.5 ng/mL. Serum procalcitonin level was correlated with the degree of fever, serum WBC, synovial fluid WBC and hs-CRP but not ESR. The correlations between these parameters are shown in Table 4.
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(a)
(b)
(c)
(d)
Figure 1 Box-plot of procalcitonin (a), high sensitivity C-reactive protein, hs-CRP (b), erythrocyte sedimentation rate, ESR (c) and synovial white blood cell count (d) in pateints with acute bacterial septic arthritis and acute non-inflammatory septic arthritis.
Table 3 Area under the curve of procalcitonin, hs-CRP, ESR and synovial fluid white blood cell count for diagnosis acute bacterial septic arthritis Variable(s) Procalcitonin Hs-CRP ESR Synovial white blood cell count
Area under the curve
95% Confidence interval
0.789 0.672 0.613 0.821
0.686–0.891 0.553–0.791 0.483–0.743 0.720–0.923
DISCUSSION Our study demonstrated that serum procalcitonin could be a potential marker for early distinction between septic and non-septic arthritis. Our study revealed similar results with previous studies8–10 in that serum procalcitonin levels were significantly higher in patients with acute bacterial septic arthritis than in patients with acute inflammatory nonseptic arthritis. However, few studies have reported that serum procalcitonin levels did not differ between patients with septic and nonseptic arthritis.11,12 Table 5 summarizes previous studies investigating the diagnostic utility of procalcitonin in acute bacterial septic arthritis. The cut-off level used for the diagnosis of septic arthritis remains uncertain. The cut-off used in our study was 0.5 ng/mL, which was used in most studies; nevertheless, the level of 0.66 ng/mL had slightly
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Figure 2 The ROC curve analysis of procalcitonin, hs-CRP and ESR for the diagnosis of acute bacterial septic arthritis.
higher specificity (86%) than the 0.5 ng/mL level (84%) with similar sensitivity (59%). Recently, metaanalysis of the diagnostic performance of serum procalcitonin in the identification of osteomyelitis and septic arthritis was investigated in patients who presented with fever and orthopedic symptoms. It was reported that the lower cut-off value of 0.2-0.3 ng/mL improved the sensitivity to 90% but had no significant
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Table 4 Correlation Coefficient of procalcitonin and other laboratory measurement Procalcitonin (ng/mL)
ESR (mm/h)
Synovial white blood cell (cell/mm3)
Serum white blood cell (cell/mm3)
Fever (°C)
1.000 –
0.451* 0.000
0.246† 0.030
0.323* 0.004
0.230† 0.045
0.451* 0.001
1.000 –
0.140 0.221
0.057 0.620
0.064 0.583
0.246† 0.030
0.140 0.221
1.000 –
0.366* 0.001
0.309* 0.006
0.323* 0.004
0.057 0.620
0.366* 0.001
1.000 –
0.140 0.223
0.230† 0.045
0.064 0.583
0.309* 0.006
0.140 0.223
1.000 –
Hs-CRP (mg/L)
Hs-CRP(mg/L) Rho 0.368* P-value 0.001 ESR (mm/h) Rho 0.157 P-value 0.174 < Synovial white blood cell (cell/mm3) Rho 0.422* P-value < 0.001 Serum white blood cell (cell/mm3) Rho 0.334* P-value 0.003 Fever (°C) Rho 0.395* P-value < 0.001
*Correlation is significant at the 0.01 level (2-tailed). †Correlation is significant at the 0.05 level (2-tailed).
Table 5 Procalcitonin levels, sensitivity and specificity in previous studies Author Butbul-Aviel Y21 Faesch et al22 Hugle et al8 Talebi-Taher et al.10 Martinot et al14 Fottner et al9 This study
Population
Number of patients
Procalcitonin (ng/mL)
Sensitivity (%)
Specificity (%)
Septic arthritis, osteomyelitis Septic arthritis, osteomyelitis Septic/non septic arthritis Septic/non septic arthritis Septic/non septic arthritis Septic/non septic arthritis Septic/non septic arthritis
42 42 42 75 42 33 78
0.5 0.5 0.25 0.5 0.5 0.5 0.5
44 25 93 68 55 53 59
100 97 93 80 94 100 84
effect on specificity (87%) and suggested that the lower cut-off should be used for localized infection such as septic arthritis.13 However, in our study a cut-off of 0.25 ng/mL provided a higher sensitivity of 78% but lower specificity of 64% with a lower overall diagnostic accuracy of 69% than a cut-off of 0.5 ng/mL. Three studies examined the role of synovial fluid procalcitonin in the diagnosis of acute bacterial septic arthritis. They found that patients with septic arthritis had significantly higher synovial fluid procalcitonin than patients with non-septic arthritis, such as rheumatoid arthritis, osteoarthritis and crystal-induced arthritis. However, serum procalcitonin performed better than synovial fluid procalcitonin in the diagnosis of septic arthritis,10,14,15 We also examined other parameters, such as hs-CRP, ESR and synovial fluid WBC, which could be helpful in diagnosing septic arthritis. Similar to previous reports,10
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we found that synovial fluid WBC performed the best and slightly better than serum procalcitonin in diagnosing septic arthritis. Thus, in patients with suspected acute bacterial septic arthritis where arthrocentesis could not be performed or in patients whose synovial fluid WBC was unreliable, such as patients given antibiotics before arthrocentesis and patients with leukopenia, serum procalcitonin could be a helpful diagnostic aid. However, if patients had concomitant infection elsewhere, for example, thyroid cancer, post-major operation and septic shock patients, serum procalcitonin could also be elevated16 and these limit the use of serum procalcitonin as a biomarker for acute bacterial septic arthritis. Our study along with previous reports demonstrated that hs-CRP is elevated in patients with septic arthritis; however, serum procalcitonin performed better in diagnosing acute bacterial septic arthritis.4,10,14 In contrast
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to other parameters, ESR did not differ between patients with and without septic arthritis and should not be used as a diagnostic tool to diagnose septic arthritis. Procalcitonin was reported to be useful in diagnosing blood stream infection, septic shock, bacteremia, community-acquired pneumonia and hospital-acquired pneumonia.2,17–19 Antibiotics treatment is strongly encouraged in communities that acquire pneumonia if procalcitonin level is greater than 0.5 ng/mL.20 Procalcitonin could be a potential useful biomarker to diagnose acute bacterial septic arthritis. The level of procalcitonin can be obtained promptly and thus, it could be used along with other clinical information to differentiate between acute bacterial septic arthritis and acute inflammatory non-septic arthritis before the result of synovial culture can be obtained. However, the costeffectiveness of using procalcitonin as a diagnostic aid for acute bacterial septic arthritis was not examined and would be interesting for future research. This study had some limitations. First, the level of serum procalcitonin decreased after the onset of bacteremia. However, in our study patients in both groups presented quite late (mean SD 6.2 3.9 days and 7.0 5.5 days for acute bacterial septic arthritis and inflammatory non-septic arthritis, respectively). Thus, serum procalcitonin was measured several days after onset of arthritis. Second, our study used Newman’s criteria to diagnose septic arthritis and synovial fluid cultures of six patients that were negative. Thus, it can be argued that these six patients really had septic arthritis.
CONCLUSION Serum procalcitonin may have a potential role in differentiating acute bacterial septic arthritis from acute inflammatory non-septic arthritis, especially in patients for whom arthrocentesis cannot be performed. It has a good diagnostic predictability for acute bacterial septic arthritis and is modestly correlated with fever, hs-CRP, serum and synovial fluid WBC.
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DISCLOSURES All authors have no conflicts of interest pertaining to this article.
REFERENCES 1 Marker-Hermann E (2008) Septic arthritis, osteomyelitis, gonococcal and syphilitic arthritis. In: Hochberg MC,
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Silman AJ, Smolen JS, Weinblatt ME, Weisman ME, eds. Rheumatology. Vol 2. 4th edn, pp 1013–28. Elsevier Limited, Spain. Seligman R, Ramos-Lima LF, Oliveira VA, Sanvicente C, Pacheco EF, Dalla Rosa K (2012) Biomarkers in community-acquired pneumonia: a state-of-the-art review. Clinics (Sao Paulo) 67, 1321–5. Muller B, Becker KL, Schachinger H et al. (2000) Calcitonin precursors are reliable markers of sepsis in a medical intensive care unit. Crit Care Med 28, 977–83. Becker KL, Snider R, Nylen ES (2010) Procalcitonin in sepsis and systemic inflammation: a harmful biomarker and a therapeutic target. Br J Pharmacol 159, 253–64. Becker KL, Nylen ES, White JC, Muller B, Snider RH Jr (2004) Clinical review 167: procalcitonin and the calcitonin gene family of peptides in inflammation, infection, and sepsis: a journey from calcitonin back to its precursors. J Clin Endocrinol Metab 89, 1512–25. Newman JH (1976) Review of septic arthritis throughout the antibiotic era. Ann Rheum Dis 35, 198–205. American College of Chest Physicians/Society of Critical Care (1992) Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 20, 864–74. Hugle T, Schuetz P, Mueller B et al. (2008) Serum procalcitonin for discrimination between septic and non-septic arthritis. Clin Exp Rheumatol 26, 453–6. Fottner A, Birkenmaier C, von Schulze Pellengahr C, Wegener B, Jansson V (2008) Can serum procalcitonin help to differentiate between septic and nonseptic arthritis? Arthroscopy 24 229–33. Talebi-Taher M, Shirani F, Nikanjam N, Shekarabi M (2013) Septic versus inflammatory arthritis: discriminating the ability of serum inflammatory markers. Rheumatol Int 33, 319–24. Lorrot M, Fitoussi F, Faye A et al. (2007) Laboratory studies in pediatric bone and joint infections. Arch Pediatr 14 (Suppl 2), S86–90. Soderquist B, Jones I, Fredlund H, Vikerfors T (1998) Bacterial or crystal-associated arthritis? Discriminating ability of serum inflammatory markers. Scand J Infect Dis 30, 591–6. Shen CJ, Wu MS, Lin KH et al. (2013) The use of procalcitonin in the diagnosis of bone and joint infection: a systemic review and meta-analysis. Eur J Clin Microbiol Infect Dis 32, 807–14. Martinot M, Sordet C, Soubrier M et al. (2005) Diagnostic value of serum and synovial procalcitonin in acute arthritis: a prospective study of 42 patients. Clin Exp Rheumatol 23, 303–10. Streit G, Alber D, Toubin MM, Toussirot E, Wendling D (2008) Procalcitonin, C-reactive protein, and complement-3a assays in synovial fluid for diagnosing septic arthritis: preliminary results. Joint Bone Spine 75, 238–9.
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16 Muller B, Christ-Crain M, Nylen ES, Snider R, Becker KL (2004) Limits to the use of the procalcitonin level as a diagnostic marker. Clin Infect Dis 39, 1867–8. 17 Kibe S, Adams K, Barlow G (2011) Diagnostic and prognostic biomarkers of sepsis in critical care. J Antimicrob Chemother 66(Suppl 2), ii33–40. 18 Polzin A, Pletz M, Erbes R et al. (2003) Procalcitonin as a diagnostic tool in lower respiratory tract infections and tuberculosis. Eur Respir J 21, 939–43. 19 Boussekey N, Leroy O, Georges H, Devos P, d’Escrivan T, Guery B (2005) Diagnostic and prognostic values of admission procalcitonin levels in community-acquired pneumonia in an intensive care unit. Infection 33, 257–63.
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20 Christ-Crain M, Stolz D, Bingisser R et al. (2006) Procalcitonin guidance of antibiotic therapy in communityacquired pneumonia: a randomized trial. Am J Respir Crit Care Med 174 (1), 84–93. 21 Butbul-Aviel Y, Koren A, Halevy R, Sakran W (2005) Procalcitonin as a diagnostic aid in osteomyelitis and septic arthritis. Pediatr Emerg Care 21, 828–32. 22 Faesch S, Cojocaru B, Hennequin C et al. (2009) Can procalcitonin measurement help the diagnosis of osteomyelitis and septic arthritis? A prospective trial. Ital J Pediatr 35 (1), 33.
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