http://informahealthcare.com/mor ISSN 1439-7595 (print), 1439-7609 (online) Mod Rheumatol, 2014; 24(3): 457–463 © 2014 Japan College of Rheumatology DOI: 10.3109/14397595.2013.844391

ORIGINAL ARTICLE

Serum procalcitonin and C-reactive protein for differentiating bacterial infection from disease activity in patients with systemic lupus erythematosus Mod Rheumatol Downloaded from informahealthcare.com by University of North Carolina on 01/20/15 For personal use only.

Jinquan Yu1, Bingling Xu2, Yuefang Huang3, Jijun Zhao1, Shuang Wang1, Hongyue Wang1, and Niansheng Yang1 1Department of Rheumatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, P. R. China, 2Department of Pulmonary Medicine,

The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, P. R. China, and 3Neonatal Intensive Care Unit, Department of Pediatrics, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, P. R. China Abstract

Keywords

Objective. To study the clinical value of procalcitonin (PCT) and C-reactive protein (CRP) in differentiating bacterial infection from disease activity in systemic lupus erythematosus (SLE) patients. Method. PCT and CRP in active SLE patients complicated with and without bacterial infection were retrospectively studied. Bacterial infection was diagnosed by positive culture results or typical symptoms and signs combined with positive response to antibiotics. Disease activity of SLE was assessed by systemic lupus erythematosus disease activity index (SLEDAI). Result. One hundred and fourteen active SLE patients were recruited, 47 of which were with bacterial infection and 67 were non-infected. PCT and CRP levels were significantly elevated in patients with bacterial infection (P ⬍ 0.05). The ideal cutoff value for PCT was 0.38 ng/ml, at which the sensitivity (74.5%) and specificity (95.5%) combined the best. The negative predictive value and positive predictive value to detect bacterial infection were 84.2% and 92.1%, respectively. PCT but not the CRP level in the septic patients was significantly higher than that of non-septic ones. Meanwhile, in patients with SLEDAI score of ⬎ 10, both PCT and CRP levels were higher in patients with bacterial infection, but the difference was only statistically significant for PCT (P ⬍ 0.05). PCT was significantly reduced after anti-bacterial treatment. Conclusion. PCT test is superior to CRP test in detecting superimposed bacterial infection in active SLE patients. The levels of PCT are correlated with the severity of bacterial infection and can be used to monitor the response to antibiotic treatment.

Bacterial infection, C-reactive protein, Disease activity, Procalcitonin, Systemic lupus erythematosus

Introduction Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with clinical features of multi-system damages. Infection is one of the major causes of death in SLE [1]. Clinical features of infection may sometimes be quite similar to those of active lupus, making it difficult to detect the existence of infection. Concurrent infection often needs antibiotic treatment with the reduction of the number or the doses of immunosuppressants, while active lupus requires upgrade of immune suppression. Considering that the therapies between infection and active lupus are completely opposite, making a correct differential diagnosis is crucial for the decision-making of treatment strategy. Biologic markers such as procalcitonin (PCT) can be used to try to distinguish between bacterial and non-bacterial infections. PCT is a peptide precursor of calcitonin that is released by parenchymal cells in response to bacterial toxins, leading to elevated serum levels in patients with bacterial infections [2,3]. Given its Correspondence to: Prof. Niansheng Yang, Department of Rheumatology, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Rd II, Guangzhou, 510080 P. R. China, Fax: ⫹ 86-20-87335784. E-mail: [email protected]

History Received 1 April 2013 Accepted 27 June 2013 Published online 18 October 2013

possibility to be detected 2 h after infection onset and return back to normal immediately after disappearance of infection, it could be applied to evaluate the progression of bacterial infection and the efficiency of anti-bacterial therapy [2]. Studies have shown that PCT can be used to help determine whether antibiotics are necessary and accordingly reduce the antibiotic exposure [4, 5]. In addition, the level of PCT was shown to correlate with severity of bacterial infection [2]. C-reactive protein (CRP) is another marker of bacterial infection and had been studied for differentiation of bacterial infection from diseased activity in SLE patients [6, 7]. However, CRP level is often elevated in many rheumatic diseases including rheumatoid arthritis, vasculitis and SLE due to autoimmune inflammation, reducing the specificity of CRP in the differential diagnosis of bacterial infection in these diseases [8]. Serum level of PCT was reported to be minimally affected by autoimmunity, so it might be a better candidate in differentiating infection from active disease in SLE patients [9, 10]. Indeed, studies had indicated that PCT was meaningful in diagnosing bacterial infection in systemic autoimmune diseases[11–13], but these studies included a mixture of various autoimmune disorders with diverse pathogenesis. So far, there are only few reports restricted to a subgroup of SLE patients. Early studies by Becker [6] and Eberhard [8] indicated

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that PCT could contribute to differentiation of bacterial infection from disease activity in SLE patients. However, there is still controversy over the usage of PCT in this group of patients. In a study by Lanoix, PCT was shown not to be able to differentiate between infection and disease flare in SLE [14]. In this study, we examined the roles of the PCT in differentiating bacterial infection from active lupus and compared the sensitivity and specificity of PCT and CRP in the recognition of bacterial infection in active SLE patients.

Patients and Methods

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Subjects Active SLE patients hospitalized for any condition in the First Affiliated Hospital of Sun Yat-sen University with complete and detailed medical records from January 2011 to June 2012 were included in this retrospective study. Diagnosis of SLE was made according to the ACR criteria for SLE [15]. The values of PCT and CRP, as well as SLEDAI score, details of infection and other clinical parameters, including gender, age, duration of SLE, complement C3 levels, anti-dsDNA levels and proteinuria were recorded. The study was approved by the Institutional Review Board of our hospital. Measurement of PCT and CRP The serum levels of CRP were measured using nephelometry immunoassay (Dade Behring Diagnostics, America), and the levels of PCT were measured using electrochemiluminescence immunoassay (Roche Diagnostics, Germany). Measurement of disease activity of SLE Disease activity was assessed using SLEDAI scores. Patients with no activity (SLEDAI score ⫽ 0) were excluded from the study. Patients with SLEDAI scores ⱕ 4, ⬎ 4, but ⱕ 10, and ⬎ 10 were defined as having mild, moderate and high disease activity, respectively [16,17]. Definition of infection The diagnosis of bacterial infection was based on the positive culture results of pathogenic microorganism. For those with negative results of microorganism culture, infection was diagnosed through typical symptoms (fever, cough, new onset of purulent sputum, urgency, frequency, dysuria, purulent drainage at affected site, etc.), signs (wheezing, rales, rhonchi, abdominal or suprapubic tenderness, etc.), radiological examination (such as evidence of an abscess on ultrasound, CT or MRI), laboratory evaluations (leukocytosis and left shift, positive urine dipstick for leukocyte esterase and/or nitrate or pyuria, etc.), and an abscess or other evidence of bacterial infection seen during a surgical operation or histopathological examination. A positive response to the standard antibacterial therapy was also used to support the diagnosis of bacterial infection. Patients with nonbacterial infection (viral and/or fungal infection) or mycobacterium tuberculosis infection were excluded from the study. Statistical analysis Statistical Package for the Social Sciences was used to perform data analyses. A chi-square test was performed to determine qualitative variables. Mann–Whitney test was used for comparing differences in data between groups. Receiver operating characteristic curves (ROC) were plotted to evaluate the diagnostic power of the PCT and CRP levels by determining the area under the curve (AUC). Sensitivity, specificity, positive and negative predictive values of PCT and CRP were also calculated. A value of P ⬍ 0.05 was considered significant, and all tests were two-tailed.

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Table 1. Demographic data and clinical characteristics of SLE patients. Clinical parameters Gender Female Male Age (years) Duration of SLE (years) SLEDAI score SLEDAI, ⬎ 4 SLEDAI, ⱕ 4 SLEDAI, ⬎ 10 SLEDAI, ⱕ 10 Complement C3 (g/L) Anti-dsDNA Proteinuria (ⱖ 3⫹)

Bacteria-infected group (n ⫽ 47)

Non-infected group (n ⫽ 67)

39 (83.0%) 8 (17.0%) 31.0 ⫾ 16.1 3.0 ⫾ 5.0

55 (82.1%) 12 (17.9%) 28.5 ⫾ 13.7 2.0 ⫾ 3.6

44 (93.6%) 3 (6.4%) 23 (48.9%) 24 (51.1%) 0.48 ⫾ 0.29 3.55 ⫾ 2.41 23 (48.9%)

64 (95.5%) 3 (4.5%) 32 (47.8%) 35 (52.2%) 0.48 ⫾ 0.29 3.67 ⫾ 2.34 24 (35.8%)

P-value 0.902 0.383 0.260 0.982 0.902 0.917 0.789 0.161

Note: The reference range of Complement C3 was 0.79–1.17 g/L and the cutoff value of anti-dsDNA was 0.90 (⬍ 0.90 as negative).

Results Patient characteristics Among a total of 114 cases recruited in this study, 47 cases were bacteria-infected and 67 cases were non-bacteria-infected (abbreviated as non-infected). There were no significant differences in demographic and clinical characteristics including gender, age, duration of SLE, SLEDAI score, complement C3 levels, antidsDNA levels and proteinuria between bacteria-infected and noninfected groups (Table 1). Type of damage and therapy of SLE patients were presented in Table 2. Site of infection and pathogenic microorganism The bacteria-infected group included 36 cases with bacterial pneumonia (6 complicated with sepsis), 9 with urinary tract infection (4 with sepsis), 4 with abdominal cavity infection (2 with sepsis), 3 with catheter-related bloodstream infection (CRBSI), 1 with cholecystitis and 1 with left pyothorax. Five cases concurrently had bacterial pneumonia and urinary tract infection (2 with sepsis) and one had cholecystitis and abdominal cavity infection simultaneously. Totally, 13 patients had sepsis. Among all bacteria-infected SLE patients, 21 positive culture results were recorded including culture of the blood, urine and sputum (Table 3). PCT and CRP in patients with bacterial infection PCT and CRP levels in the bacteria-infected or non-infected groups were presented in Figure 1A. Both PCT and CRP levels of Table 2. Type of damage and therapy of SLE patients. Type of damage and therapy Type of damage Rash Oral ulcer Joint Nephritis Neuropsychiatric lupus Lung Involvement Therapy Glucocorticoid Cyclophosphamide Cyclosporine A Mycophenolate mofetil Methotrexate Hydroxychloroquine

Bacteria-infected group (n ⫽ 47)

Non-infected group (n ⫽ 67)

21 (44.7%)NS 25 (53.2%)* 14 (29.8%)NS 28 (59.6%)NS 3 (6.4%)NS 2 (4.3%)NS

28 (41.8%) 20 (29.9%) 30 (44.8%) 30 (44.8%) 7 (10.4%) 3 (4.5%)

34 (72.3%)* 7 (14.9%)NS 4 (8.5%)NS 4 (8.5%)* 3 (6.4%)NS 9 (19.1%)NS

36 (53.7%) 11 (16.4%) 6 (9.0%) 0 (0%) 2 (3.0%) 18 (26.9%)

Note: *P ⬍ 0.05, NSP ⬎ 0.05, compared to the non-infected group.

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Table 3. The affected sites, pathogenic microorganisms and PCT level in SLE patients. Pathogens Acinetobacter baumannii Acinetobacter baumannii Acinetobacter baumannii Acinetobacter baumannii Acinetobacter baumannii Acinetobacter baumannii Escherichia coli Escherichia coli Escherichia coli Escherichia coli Pseudomonas aeruginosa Stenotrophomonas maltophilia Kocuria kristinae Burkholderia cepacia Salmonella cholerae-suis Enterococcus faecium Enterococcus faecalis Staphylococcus aureus Enterococcus gallinarum Micrococcus luteus Viridans streptococcus

Culture Blood Blood Blood Sputum Sputum Sputum Blood Blood Blood Blood Sputum Sputum Blood Blood Blood Urine Urine Sputum Blood Sputum Sputum

Infection site Lung and UTI Lung and UTI Lung Lung Lung Lung Abdominal cavity Abdominal cavity Urinary tract Urinary tract Lung Lung CRBSI CRBSI CRBSI Lung and Urinary tract Lung and Urinary tract Lung Lung Lung Lung

Sepsis (Y/N) Y Y Y N N N Y Y Y Y N Y Y Y Y N N Y Y N N

PCT (ng/ml) 2.16 8.54 4.25 1.60 0.65 0.62 1.44 12.07 1.50 41.88 0.05 2.00 2.51 1.07 7.94 2.00 0.65 17.64 14.08 0.05 0.50

Note: UTI, urinary tract infection; and CRBSI, catheter-related bloodstream infection.

bacteria-infected group were significantly higher than those of the non-infected group, respectively (P ⬍ 0.05). We compared bacteria-infected group with non-infected group, and plotted ROC curves accordingly to obtain the cutoff value of PCT and CRP to diagnose bacterial infection (Figure 2). The cutoff value for PCT was 0.38 ng/ml, at which sensitivity (74.5%) and specificity (95.5%) had the best combination, while the positive predictive value (PPV) and negative predictive value (NPV) were 92.1% and 84.2%, respectively. A cutoff level of 0.71 mg/dl for CRP was with 70.2% sensitivity and 62.7% specificity. The PPV and NPV were 56.9% and 75.0%, respectively, for CRP (Table 4). The area under the ROC curves (AUC; 95% CI) for PCT and CRP was 0.896 (0.829–0.963) versus 0.698 (0.600–0.795), respectively, with significant difference (P ⬍ 0.05). There were only three cases of non-infected patients whose PCT level was above the cutoff level of 0.38 ng/ml, and their detailed characteristics were listed in Table 5. PCT and CRP levels in SLE patients with sepsis To see whether the levels of PCT in active SLE patients were associated with severity of infection, we compared the subgroup of sepsis with the non-sepsis patients. PCT levels in sepsis patients were significantly higher than those of non-septic ones (Figure 1B). In contrast, there was no significant difference in CRP level between patients with or without sepsis. Furthermore, we compared subgroups of bacterial infection with and without sepsis and then plotted ROC curve to determine the cutoff value of PCT in diagnosing sepsis (Figure 3). When the cutoff value was set at 1.06 ng/ml, the sensitivity and specificity of PCT to diagnose sepsis were 100% and 76.5%, respectively. When the cutoff value was set at higher value of 2.13 ng/ml, the specificity went up to 100% and the sensitivity was reduced to 69.2%. PCT and CRP levels in febrile patients Among all 114 cases of our study, 83 patients (72.8%) were febrile, 43 of which were bacteria-infected and 40 were non-infected. Differentiation between infection and active lupus is challenging in the febrile SLE patients. To examine whether PCT is of help in the differential diagnosis, we compared the PCT and CRP levels in these patients. The results indicated that both PCT and CRP levels

in febrile bacteria-infected patients were significantly higher than those of the non-infected patients (Figure 1C). PCT and CRP levels in patients with SLEDAI Score of ⬎ 10 Patients with active disease of SLE might have great impacts on the PCT or CRP because of elevated levels of autoimmune inflammatory response. To examine whether PCT or CRP can assist in detection of the complicated infection in patients with different activity, we compared the PCT or CRP level between the bacteria-infected and the non-infected patients in a subgroup of patients with a SLEDAI score of ⬎ 4 and then in a subgroup of patients with a SLEDAI score of ⬎ 10. In patients with SLEDAI score of ⬎ 4, both PCT and CRP levels were significantly higher in bacteria-infected patients than those in non-infected group (Figure 1D). In contrast, the difference was only statistically significant in PCT level but not in CRP level of patients with a SLEDAI score of ⬎ 10 (Figure 1E). Comparison of PCT levels before and after treatment In bacteria-infected group, 12 patients had sequential measurement of PCT before and after anti-bacterial treatment. The PCT levels before treatments were 4.79 ⫾ 6.44 ng/ml, which was significantly reduced to 0.67 ⫾ 1.71 ng/ml after treatment (P ⬍ 0.05).

Discussion PCT is produced in response to endotoxin or to the released mediators such as IL-1β induced by bacterial infections [18]. On the other hand, upregulation of PCT is attenuated by interferon-γ (INF-γ) [18]. INF-γ released in response to viral infections offsets the role of IL-1β in the induction of PCT. This helps to explain why PCT is more specific to bacterial infections and may help to distinguish bacterial infections from viral illnesses [19]. In the autoimmune diseases, the expression of a variety of cytokines is upregulated [20, 21]. However, elevated PCT levels have not been noted for autoimmune disease process, including inflammatory bowel disease, temporal giant cell arteritis, polyarteritis nodosa, gout and Still’s disease [13, 22, 23]. Furthermore, PCT levels are not influenced by glucocorticoids or nonsteroidal antiinflammatory agents [24, 25].

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Figure 1. PCT and CRP in SLE patients with bacterial infection. (A) Comparison of PCT and CRP levels between bacteria-infected group (n ⫽ 47) and non-bacteria-infected (abbreviated as non-infected) group (n ⫽ 67). (B) Comparison of PCT and CRP levels between SLE patients with (n ⫽ 13) and those without sepsis (n ⫽ 34). (C) Comparison of PCT and CRP levels between febrile SLE patients with (n ⫽ 43) and those without bacterial infection (n ⫽ 40). (D) Comparison of PCT and CRP levels between SLE patients of SLEDAI score of ⬎ 4 with (n ⫽ 44) and without bacterial infection (n ⫽ 64). E: Comparison of PCT and CRP levels between SLE patients of SLEDAI score of ⬎ 10 with (n ⫽ 23) and without bacterial infection (n ⫽ 32). *P ⬍ 0.05, **P ⬍ 0.01, and NSP ⬎ 0.05.

There were quite a few reports describing the role of PCT or CRP as a biomarker of infection in autoimmune diseases [26]. A meta-analysis of these studies showed that the pooled sensitivity was 77% and the pooled specificity was 56% for CRP, while the pooled sensitivity was 75% and the pooled specificity was 95% for PCT [26]. The author concluded that test for PCT is more specific than sensitive. However, these studies included a heterogeneous collection of rheumatic diseases including rheumatoid arthritis, Still’s disease, vasculitis and SLE. CRP level tends to be elevated

in diseases like rheumatoid arthritis, Still’s disease and vasculitis even without superimposed infection. Results from studies recruiting SLE patients only were conflicting. Bador et al. [27] reported that PCT but not CRP level was higher with infection in lupus flare patients, and suggested that serum PCT is more reliable in ruling out bacterial infection in active SLE. On the contrary, Lanoix et al. [14] showed that serum PCT does not differentiate between infection and disease flare in patients with SLE. In another report, Quintana et al. [10] concluded that SLE activity does not increase

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Table 4. Sensitivity, Specificity, PPV and NPV of PCT and CRP to diagnose bacterial infection. Parameters PCT CRP

Sensitivity 74.5% 70.2%

Specificity 95.5% 62.7%

PPV 92.1 56.9%

NPV 84.2% 75.0%

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Note: PPV, positive predictive value; NPV, negative predictive value.

Figure 2. ROC curves of PCT and CRP in SLE patients. ROC curves comparing sensitivity and specificity of PCT and CRP levels to diagnose bacterial infection (47 with bacterial infection and 67 without infection). The cutoff value for PCT and CRP levels were 0.38 ng/ml and 0.71 mg/dl, respectively.

serum PCT level but its increase does suggest a concurrent bacterial or mycotic infection. However, this study did not include a cohort of patients with both active SLE and infection. Only three patients with frankly elevated PCT levels had active disease (one with pneumonia, one with renal failure and the other with urinary tract infection), and none have severe bacterial infection. In the present study, we examined the PCT and CRP levels in active SLE patients with or without concurrent bacterial infections. Our results revealed that PCT and CRP values of bacteriainfected SLE patients were significantly higher than those of non-infected patients, suggesting that both PCT and CRP can be used to identify superimposed infection from the active disease of SLE itself, which was further confirmed by calculating the areas under the ROC curves. The cutoff values were 0.38 ng/ml for PCT and 0.71 mg/dl for CRP, at which sensitivity and specificity combined the best. On the basis of these cutoff values, the sensitivities of PCT and CRP were both above 70%, while PCT had better specificity (95.5%) than CRP (62.7%), indicating that PCT is superior to CRP in the differential diagnosis of bacterial infection. Moreover, the positive predictive value of PCT was up to 92.1% in our series, indicating the excellent ability of PCT test in diagnosing bacterial infection in addition to its high specificity. Our results are consistent with those of the study by Kim et al. [28], who showed significantly higher CRP or PCT levels in SLE patients with infection than in patients with flare but no evidence of infection. Furthermore, PCT level was significantly higher in patients with sepsis. They found that PCT had a lower sensitiv-

ity (38.2% vs 100%) but higher specificity (93.3% vs 90%). The authors attributed the low sensitivity of PCT to the inclusion of patients with localized infection, and suggested that PCT can be used for determining the presence of sepsis. In this study, we set a PCT cutoff level at 0.38 ng/ml for the diagnosis of infection but not for sepsis in SLE. Bador et al. [27] set an even lower cutoff value of PCT as 0.12 ng/ml with sensitivity of 80% and specificity of 78%. Though their sensitivity was slightly higher than that of 0.38 ng/ml as cutoff value in our study (80% vs 74.5%), their specificity with PCT value of 0.12 ng/ml was considerably lower than ours at 0.38 ng/ml (78% vs 95.5%). Our results showed that such a cutoff value of 0.38 ng/ml has a balanced sensitivity and specificity according to the ROC curve. PCT was shown to correlate with the severity of communityacquired pneumonia [29]. In one study of severe community-acquired pneumonia, PCT levels increased over time in non-survivors but decreased in survivors [30]. It is interesting to see whether the sepsis, a state of severe infection, affects the PCT level in SLE. We found that PCT levels were significantly higher in bacterial-infected patients complicated with sepsis than in those without sepsis. In contrast, there was no significant difference in the levels of CRP between the patients with and without sepsis. These results demonstrated that PCT correlated with severity of infection better than CRP in SLE complicated with infection and can be used to identify the patients critically infected by bacteria. Considering the 100% sensitivity of 1.06 ng/ml as cutoff value of PCT and 100% specificity of 2.13 ng/ml, we would recommend using these two values to rule out or to diagnose sepsis, respectively. As for the PCT level between 1.06 and 2.13 ng/ml, diagnosis of sepsis should be made on the combination of clinical features and other relevant evidences. It is a challenge to differentiate whether the cause of a fever is due to superimposed infection or to the disease activity of SLE itself. Our data showed that both PCT and CRP levels were significantly elevated during bacterial infection, indicating that PCT and CRP can be used in the differential diagnosis of bacterial infection in febrile patients. Furthermore, in patients responded positively to the antibiotic therapies, PCT levels were significantly reduced following treatment, suggesting that PCT is also useful in monitoring the response of antibiotic treatment in these SLE patients. It is interesting to discuss whether disease activity can affect the diagnostic value of PCT and CRP. We used a cutoff SLEDAI score of ⬎ 4 to indicate moderate disease activity. Both the levels of PCT and CRP were significantly higher in the bacterial-infected patients. In the more active patients with SLEDAI score of ⬎ 10 [17], both levels of PCT and CRP were higher in the bacterialinfected patients, but the difference was only significant for PCT

Table 5. Characteristics of non-infected patients with high PCT level. Patient No.1 No. 2 No. 3

Age (years) 19 54 14

Gender Female Male Male

Type of damage Skin, joint Skin Kidney (Pro 4⫹, SCr ⫽ 210 μmol/L)

SLEDAI score 11 8 12

C3 (g/L) 0.22 0.06 0.32

PCT (ng/ml) 0.50 0.91 1.86

Note: GCs, glucocorticoids; Pro, proteinuria; SCr, serum creatinine; and CTX, cyclophosphamide.

Therapy GCs GCs GCs ⫹ CTX

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References

Figure 3. ROC curve of PCT in bacteria-infected SLE patients. ROC curve of PCT was plotted for setting diagnostic cutoff value for sepsis in bacteria-infected SLE patients. When the cutoff value was 1.06 ng/ml, the sensitivity and specificity of PCT to diagnose sepsis were 100% and 76.5%, respectively. If the cutoff value was 2.13 ng/ml, the specificity went to 100% and sensitivity was 69.2%.

but not for CRP, suggesting that PCT is especially helpful in diagnosing bacterial infection in very active SLE patients. Although complement is an acute-phase protein for inflammation and could be elevated during bacterial infection, no difference in complement level was found between the bacteria-infected and the non-infected groups in our study. In comparison with CRP, complement C3 increased only very modestly and slowly during acute inflammation, making it less useful as a marker of the acute-phase reactant [31]. Moreover, increased consumption during active lupus confounds its application in monitoring infection in SLE. The present study had a few limitations. First, this study is retrospective in nature and only some of the patients with bacterial infection subjected to serial measurement of PCT. Second, in the hospitalized patients, PCT was monitored mostly when the infection was considered and the absence of PCT test in patients without suspicions would cause the bias. Further prospective study with serial measurement of PCT would present more comprehensive evidences.

Conclusion PCT test is superior to CRP test in detecting superimposed bacterial infections in active SLE patients. The levels of PCT are correlated with the severity of bacterial infection and can be used to monitor the response to antibiotic treatment.

Funding This project was supported by a grant from the National Natural Science Foundation (81273278), grants from the Natural Science Foundation of Guangdong Sciences Committee (s2011010004578 and S2012010008780), and a grant from the Guangzhou Science and Technology program (2012J4100085).

Conflict of interest None.

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Serum procalcitonin and C-reactive protein for differentiating bacterial infection from disease activity in patients with systemic lupus erythematosus.

To study the clinical value of procalcitonin (PCT) and C-reactive protein (CRP) in differentiating bacterial infection from disease activity in system...
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