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Procalcitonin for the early discrimination of fever etiology in patients with systemic autoimmune diseases attending the emergency department

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Abstract

In febrile patients with known systemic autoimmune disease, early discrimination between infection and disease flare often represents a clinical challenge. This study aimed at evaluating the efficacy of procalcitonin (PCT) and other common inflammatory biomarkers in discriminating disease flare from bacterial infections in the Emergency Department (ED). In a cross-sectional observational retrospective study, we identified consecutive febrile patients with a known diagnosis of systemic autoimmune disease, admitted to the ED, and subsequently hospitalized. Flare vs infective disease was defined on clinical records at hospital discharge. Dosage of common inflammatory markers was performed at ED admission. Out of 177 patients, those with infection were most commonly elderly, frail, and with reduced peripheral oxygen saturation at admission. When compared to C-reactive protein (CRP) and white blood count (WBC), PCT showed the best performance in discriminating infections vs flare. However, only at a very high threshold value of 2 ng/ml, the PCT had a satisfactory negative predictive value of 88.9%, although with a very low specificity of 13.6% and a positive predictive value of 35.8%. Our data suggest that in the ED setting, the early PCT determination has low accuracy in the differentiation of disease flare from infection in patients with known rheumatologic disease. However, the PCT could be useful in elderly and comorbid subjects, in supporting clinical assessment and in recognizing those febrile patients needing prompt antibiotic treatment.

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Data Avaibility Statement

The data presented in this study are available on reasonably request from the corrisponding author.

References

  1. El-Serougy E, Zayed HS, Ibrahim NM, Maged LA (2019) Procalcitonin and C-reactive protein as markers of infection in systemic lupus erythematosus: the controversy continues. Lupus 28:1328–1336

    Article  Google Scholar 

  2. Buhaescu I, Yood RA, Izzedine H (2010) Serum procaclcitonin in systemic autoimmune diseases-whre are we now? Semin Arthritis Rheum 40:176–183

    Article  CAS  PubMed  Google Scholar 

  3. Sciascia S, Ceberio L, Garcia-Fernandez C, Roccatello D, Karim Y, Cuadrado MJ (2012) Systemic lupus erythematosus and infections: clinical importance of conventional and upcoming biomarkers. Autoimmun Rev 12:157–163

    Article  CAS  PubMed  Google Scholar 

  4. Ospina FE, Echeverri A, Zambrano D, Suso JP, Martínez-Blanco J, Cañas CA, Tobón GJ (2017) Distinguishing infections vs flares in patients with systemic lupus erythematosus. Rheumatology (Oxford) 56(1):i46–i54

    CAS  PubMed  Google Scholar 

  5. Liu LN, Wang P, Guan SY, Li XM, Li BZ, Leng RX, Pan HF (2017) Comparison of plasma/serum levels of procalcitonin between infection and febrile disease flare in patients with systemic lupus erythematosus: a meta-analysis. Rheumatol Int 37:1991–1998

    Article  CAS  PubMed  Google Scholar 

  6. Serio I, Arnaud L, Mathian A, Hausfater P, Amoura Z (2014) Can procalcitonin be used to distinguish between disease flare and infection in patients with systemic lupus erythematosus: a systematic literature review. Clin Rheumatol 33:1209–1215

    Article  PubMed  Google Scholar 

  7. Becker KL, Nylén ES, White JC, Müller B, Snider RH Jr (2004) 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 89:1512–1525

    Article  CAS  PubMed  Google Scholar 

  8. Simon L, Gauvin F, Amre DK, Saint-Louis P, Lacroix J (2004) Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis. Clin Infect Dis 39:206–217

    Article  CAS  PubMed  Google Scholar 

  9. Becker KL, Snider R, Nylen ES (2008) Procalcitonin assay in systemic inflammation, infection, and sepsis: clinical utility and limitations. Crit Care Med 36:941–952

    Article  CAS  PubMed  Google Scholar 

  10. Limper M, de Kruif MD, Duits AJ, Brandjes DP, van Gorp EC (2010) The diagnostic role of procalcitonin and other biomarkers in discriminating infectious from noninfectious fever. J Infect 60:409–416

    Article  CAS  PubMed  Google Scholar 

  11. Tamaki K, Kogata Y, Sugiyama D, Nakazawa T, Hatachi S, Kageyama G, Nishimura K, Morinobu A, Kumagai S (2008) Diagnostic accuracy of serum procalcitonin concentrations for detecting systemic bacterial infection in patients with systemic autoimmune diseases. J Rheumatol 35:114–119

    CAS  PubMed  Google Scholar 

  12. Scirè CA, Cavagna L, Perotti C, Bruschi E, Caporali R (2006) Montecucco C Diagnostic value of procalcitonin measurement in febrile patients with systemic autoimmune diseases. Clin Exp Rheumatol 24:123–128

    PubMed  Google Scholar 

  13. Chen DY, Chen YM, Ho WL, Chen HH, Shen GH, Lan JL (2009) Diagnostic value of procalcitonin for differentiation between bacterial infection and non-infectious inflammation in febrile patients with active adult-onset Still’s disease. Ann Rheum Dis 68:1074–1075

    Article  PubMed  Google Scholar 

  14. Yu J, Xu B, Huang Y, Zhao J, Wang S, Wang H, Yang N (2014) Serum procalcitonin and C-reactive protein for differentiating bacterial infection from disease activity in patients with systemic lupus erythematosus. Mod Rheumatol 24:457–463

    Article  CAS  PubMed  Google Scholar 

  15. Gowin E (2016) Wysocki J Limited diagnostic value of procalcitonin in early diagnosis of adult onset Still’s disease. Reumatologia 54:207–211

    Article  PubMed  PubMed Central  Google Scholar 

  16. Beça S, Rodríguez-Pintó I, Alba M, Cervera R, Espinosa G (2015) Development and validation of a risk calculator to differentiate flares from infections in systemic lupus erythematosus patients with fever. Autoimmun Rev 14:586–593

    Article  PubMed  Google Scholar 

  17. Li Z, **ao Y, Zhang L (2020) Application of procalcitonin, white blood cell count and neutrophil-to-lymphocyte ratio in the diagnosis of systemic lupus erythematosus with a bacterial infection. Ann Palliat Med 9:3870–3876

    Article  PubMed  Google Scholar 

  18. Zhai X, Feng M, Guo H, Liang Z, Wang Y, Qin Y, Wu Y, Zhao X, Gao C, Luo J (2021) Development of Prediction Models for New Integrated Models and a Bioscore System to Identify Bacterial Infections in Systemic Lupus Erythematosus. Front Cell Infect Microbiol 11:620372

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Charlson ME, Pompei P, Ales KL, MacKenzie CR (1987) A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 40:373–383

    Article  CAS  PubMed  Google Scholar 

  20. Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH (1992) Derivation of the SLEDAI: a disease activity index for lupus patients. Comm Progn Stud SLE 35:630–640

    CAS  Google Scholar 

  21. Myasoedova E, De Thurah A, Erpelding ML, Schneeberger EE, Maribo T, Citera G, Davis JM, Matteson EL, Crowson CS, Fautrel B, Guillemin F (2020) Definition and construct validation of clinically relevant cutoffs on the Flare Assessment in Rheumatoid Arthritis (FLARE-RA) questionnaire. Semin Arthritis Rheum 50:261

    Article  PubMed  Google Scholar 

  22. Lawton G, Bhakta BB, Chamberlain MA, Tennant A (2004) The Behçet’s disease activity index. Rheumatology (Oxford) 43:73–78

    Article  CAS  PubMed  Google Scholar 

  23. Seror R, Ravaud P, Bowman SJ, Baron G, Tzioufas A, Theander E et al (2010) EULAR Sjögren’s syndrome disease activity index (ESSDAI): development of a consensus systemic disease activity index for primary Sjögren’s syndrome. Ann Rheum Dis 69:1103–1109

    Article  PubMed  Google Scholar 

  24. Valentini G, Della Rossa A, Bombardieri S, Bencivelli W, Silman AJ, D’Angelo S et al (2001) European multicenter study to define disease activity criteria for systemic sclerosis: II. identification of disease activity variables and development of preliminary activity indexes. Ann Rheum Dis 60:592–598

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Luqmani RA, Bacon PA, Moots RJ, Janssen BA, Pall A, Emery P et al (1994) Birmingham vasculitis activity score (BVAS) in systemic necrotizing vasculitis. QJM 87:671–678

    CAS  PubMed  Google Scholar 

  26. DeWitt S, Chavez SA, Perkins J, Long B, Koyfman A (2017) Evaluation of fever in the emergency department. Am J Emerg Med 35:1755–1758

    Article  PubMed  Google Scholar 

  27. Makam AN, Auerbach AD, Steinman MA (2014) Blood culture use in the emergency department in patients hospitalized for community-acquired pneumonia. JAMA Intern Med 174:803–806

    Article  PubMed  PubMed Central  Google Scholar 

  28. Shi Y, Peng JM, Hu XY, Wang Y (2015) The utility of initial procalcitonin and procalcitonin clearance for prediction of bacterial infection and outcome in critically ill patients with autoimmune diseases: a prospective observational study. BMC Anesthesiol 15:137

    Article  PubMed  PubMed Central  Google Scholar 

  29. Covino M, Gallo A, Montalto M, De Matteis G, Burzo ML, Simeoni B, Murri R, Candelli M, Ojetti V, Franceschi F (2021) The role of early procalcitonin determination in the emergency departiment in adults hospitalized with fever. Medicina (Kaunas) 57:179

    Article  PubMed  Google Scholar 

  30. van der Does Y, Limper M, Jie KE, Schuit SCE, Jansen H, Pernot N et al (2018) Procalcitonin-guided antibiotic therapy in patients with fever in a general emergency department population: a multicentre non-inferiority randomized clinical trial (HiTEMP study). Clin Microbiol Infect 24:1282

    Article  PubMed  Google Scholar 

  31. van der Does Y, Rood PPM, Ramakers C, Schuit SCE, Patka P, van Gorp ECM, Limper M (2018) Identifying patients with bacterial infections using a combination of C-reactive protein, procalcitonin, TRAIL, and IP-10 in the emergency department: a prospective observational cohort study. Clin Microbiol Infect 24:1297

    Article  PubMed  Google Scholar 

  32. de Jong E, van Oers JA, Beishuizen A, Vos P, Vermeijden WJ, Haas LE et al (2016) Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial. Lancet Infect Dis 16:819

    Article  PubMed  Google Scholar 

  33. Schuetz P, Wirz Y, Sager R, Christ-Crain M, Stolz D, Tamm M et al (2018) Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis. Lancet Infect Dis 18:95

    Article  CAS  PubMed  Google Scholar 

  34. Alba GA, Truong QA, Gaggin HK, Gandhi PU, De Berardinis B, Magrini L et al (2016) Global Research on Acute Conditions Team (GREAT) network diagnostic and prognostic utility of procalcitonin in patients presenting to the emergency department with dyspnea. Am J Med 129:96

    Article  CAS  PubMed  Google Scholar 

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Funding

This research received no external funding.

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Authors and Affiliations

  1. Fondazione Policlinico Universitario A. Gemelli, IRCCS, Largo A. Gemelli 1, 00168, Rome, Italy

    Marcello Covino, Antonella Gallo, Benedetta Simeoni, Celeste Ambra Murace, Francesca Ibba, Erika Pero, Francesco Franceschi, Francesco Landi & Massimo Montalto

  2. Università Cattolica del Sacro Cuore, Rome, Italy

    Francesco Franceschi, Francesco Landi & Massimo Montalto

Authors
  1. Marcello Covino
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  2. Antonella Gallo
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  3. Benedetta Simeoni
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  4. Celeste Ambra Murace
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  5. Francesca Ibba
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  6. Erika Pero
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  7. Francesco Franceschi
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  8. Francesco Landi
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  9. Massimo Montalto
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Contributions

MC, AG, MMo, study concept and design; all authors involved in the acquisition of data; BS, CAM, FI, FF, analysis and interpretation of data; MC, AG, EP, MM, FL, drafting of the manuscript. All authors were involved in the critical revision of the manuscript for important intellectual content. All authors approved the final version of the manuscript.

Corresponding author

Correspondence to Antonella Gallo.

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The authors declare no conflict of interest.

Human and animal rights and Informed consent

This study was conducted according to the principles expressed in the Declaration of Helsinki and its later amendments, and approved by local Institutional Review Board (0051814/19). Being a retrospective study performed on a database of anonymized patients, patients's informed consent was waived.

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Covino, M., Gallo, A., Simeoni, B. et al. Procalcitonin for the early discrimination of fever etiology in patients with systemic autoimmune diseases attending the emergency department. Intern Emerg Med 18, 617–625 (2023). https://doi.org/10.1007/s11739-022-03154-y

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  • DOI: https://doi.org/10.1007/s11739-022-03154-y

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