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Causes of fever and value of C-reactive protein and procalcitonin in differentiating infections from paraneoplastic fever.

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The aims of our retrospective study were to study first the causes of 245 febrile episodes in cancer patients and then the value of procalcitonin (PCT) and C-reactive protein (CRP) in differentiating infections from paraneoplastic fever.


The causes of fever were studied in 245 consecutive cases observed between January and December 2002, and PCT and CRP diagnostic value in 155 cases (114 infections and 41 paraneoplastic fever).


The two main causes of fever were infection (121 cases) and paraneoplastic fever (43 cases); 77 infections were microbiologically documented. Cocci gram positive caused 41 out of 77 documented infections. Paraneoplastic fever was more frequent in metastatic disease (p=6.10-6). CRP and PCT serum levels at admission did not differ significantly in the infection group and paraneoplastic fever group (respectively p=0.39 and p=0.14 with Mann-Whitney test). The PCT and CRP levels had poor prognostic value in infection (respectively 0.04 and 0.0003 with Mann-Whitney test).


Causes of fever are very numerous in cancer patients (more than 75 different causes in this study). Bacterial infection is the most frequent cause. PCT and CRP failed to discriminate infection, but both had pejorative prognostic value in infected patients.

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  1. Al-Nawas B, Shah PM (1996) Procalcitonin in patients with and without immunosuppression and sepsis. Infection 24:434–436

    PubMed  Google Scholar 

  2. Barnes C, Ignjatovic V, Newall F, Carlin J, Ng F, Hamilton S, Ashley D, Waters K, Monagle P (2002) Change in serum procalcitonin (delta PCT) predicts, the clinical outcome of children admitted with febrile neutropenia. Br J Haematol 118:1197–1198

    Article  PubMed  Google Scholar 

  3. Baumel H, Deixone B, Bruel JM, Dubois A, Lopez C, et al(1987) Cancers du pancréas exocrine. In In Cancers Digestifs. Zeintoun P, eds. Paris, Flammarion Médecine-Sciences, 317–388

  4. Bernard L, Ferriere F, Casassus P, et al (1998) Procalcitonin as an early marker of bacterial infection in severely neutropenic febrile adults. Clin Infect Dis 27:914–915

    CAS  PubMed  Google Scholar 

  5. Blay JY, Rossi JF, Wijdenes J, Menetrier-Caux C, Scheman S, Negrier S, Philip T, Favrot M (1997) Role of interleukin-6 in the paraneoplastic inflammatory syndrome associated with renal-cell carcinoma. Int J Cancer 72:424–430

    Article  CAS  PubMed  Google Scholar 

  6. Blijlevens NM, Donnely JP, Meis JF, DE Keizer MH, De Pauw BE (2000) Procalcitonin does not discriminate infection from inflammation after allogenic marrow transplantation. Clin Diagn Lab Immunol 7:889–892

    Article  CAS  PubMed  Google Scholar 

  7. Boggs DR, Frei E III (1960) Clinical studies of fever and infection in cancer. Cancer 13:1240–1253

    Google Scholar 

  8. Borries-Azeau A, Givarc’h B (1981) 683 tumeurs rétropéritonéales primitives. In: Martin C (ed) Rapport du 83éme congrès de Chirurgie. Masson, Paris

  9. Browder AA, Huff JW, Petersdorf RG (1965) The significance of fever in neoplastic disease. Ann Intern Med 55:932–949

    Google Scholar 

  10. Chang JC (1989) Neoplastic fever, a proposal for diagnosis. Arch Intern Med 149:1728–1730

    Article  CAS  PubMed  Google Scholar 

  11. Dandonna P, Nix D, Wilson MF, Aljata A, Love J, Assicot M (1994) Procalcitonin increase after endotoxin infections in normal subjects. J Clin Endocrinol Metabol 79:1605–1608

    CAS  Google Scholar 

  12. Engel A, Mack E, Kern P, Kern WV (1998) An analysis of interleukin-8, interleukin-6 and C-reactive protein serum concentrations to predict fever, gram-negative bacteriemia and complicated infection in neutropenic cancer patients. Infection 26:213–221

    CAS  PubMed  Google Scholar 

  13. Engel A, Steinbach G, Kern P, Kern WV (1999) Diagnostic value of procalcitonin serum levels in neutropenic patients with fever: comparison with interleukin-8. Scand J Infect Dis 31:185–189

    CAS  PubMed  Google Scholar 

  14. Fenster LF, Klastin G (1961) Manifestations of metastatic tumours of the liver. Am J Med 31:238–248

    CAS  PubMed  Google Scholar 

  15. Fleischack G, Kambeck I, Cipic D, Hassan C, Bode U (2000) Procalcitonin in pediatric cancer patients: its diagnostic relevance is superior to that of C-reactive protein, interleukin 6, interleukin 8, soluble interleukin 2 receptor and soluble tumour necrosis factor receptor II. Br J Haematol 111:1093–1102

    Article  CAS  PubMed  Google Scholar 

  16. Gendrel D, Raymond J, Assicot M, Moulin F, Iniguez JL, Lebon P, et al (1997) Measurement of procalcitonin levels in children with bacterial or viral meningitis. Clin Infect Dis 41:832–40

    Google Scholar 

  17. Gerard Y, Hober D, Assicot M, Alfandari S, Ajana F, Bourez JM, et al (1997) Procalcitonin as a marker of bacterial sepsis in patients infected with HIV-1. J Infect 35:41–46

    CAS  PubMed  Google Scholar 

  18. Ghillani PP, Motte P, Troalen F, Julienne A, Gardet P, Le Chevalier T, et al (1989) Identification and measurement of calcitonin precursors in serum of patients with malignant diseases. Cancer Res 49:6845–6851

    CAS  PubMed  Google Scholar 

  19. Giamarellos-Bourboulis EJ, Grecka P, Poulajou G, Anargyrou K, Katsilambros N, Giamarellou H (2001) Assessment of procalcitonin as a diagnostic marker of underlying infection in patients with febrile neutropenia. Clin Infect Dis 32:1718–1728

    CAS  PubMed  Google Scholar 

  20. Giamarellos-Bourboulis EJ, Mega A, Grecka P, Scarpa N, Koratzanis G, Thomopoulos G, Giamarellou H (2002) Procalcitonin:a marker to clearly differentiate systemic inflammatory response syndrome and sepsis in the critically ill patient? Intensive Care Med 28:1351–1356

    Article  Google Scholar 

  21. Kallio R, Surcel HM, Bloigu A, Syrjala H (2000) C-reactive protein, procalcitonin and interleukin-8 in the primary diagnosis of infections in cancer patients. Eur J Cancer 889–894

  22. Kallio R, Bloigu A, Surcel HM, Syrjala H (2001) C-reactive protein and erythrocyte sedimentation rate in differential diagnosis between infections and neoplastic fever in patients with solid tumours and lymphomas. Support Care Cancer 9:124–128

    Article  CAS  PubMed  Google Scholar 

  23. Klastersky J, Weerts D, Hensgens C, Debusscher L (1973) Fever of unexplained origin in patients with cancer. Eur J Cancer 9:649–656

    CAS  PubMed  Google Scholar 

  24. Lestin F, Lestin HG, Burstein C, Anders O, Freund M (1998) Provisional experience with procalcitonin, C-reactive protein, neopterin, selected cytokines and hemostatic parameters in patients with malignant hematological diseases and febrile neutropenia induced by cytostatic treatment. Clin Lab 44:451–461

    CAS  Google Scholar 

  25. Penel N, Fournier C, Degardin M, Kouto H, N’Guyen M (2001) Fièvre et tumeur solide: valeur diagnostique de la procalcitonine et de la protéine C réactive. Rev Med Interne 22:706–714

    Article  CAS  PubMed  Google Scholar 

  26. Pizzo PA, Robichaud KJ, Wasley R (1982) Fever in pediatric and young adults with cancer. A prospective study of 1001episodes. Medicine 61:153–165

    CAS  PubMed  Google Scholar 

  27. Rau B, Steinbach G, Gansauge F, Mayer JM, Grunert A, Berger HG (1997) The potential role of procalcitonin and interleukin 8 in the prediction of infected necrosis in acute pancreatitis. Gut 41:832–840

    CAS  PubMed  Google Scholar 

  28. Richie AWS, de Kernion JB (1987) The natural history and clinical features of renal carcinoma. Semin Nephrol 7:131–135

    PubMed  Google Scholar 

  29. Rosenberg SA, Diamond HD, Jaslowitz B, Crower LF (1961) Lymphosarcoma: a review of 1269 cases. Medicine 40:31–39

    CAS  Google Scholar 

  30. Ruokonen E, Nousianen T, Pulkki K, Takala J (1999) Procalcitonin concentrations in patients with neutropenic fever. Eur J Clin Microbiol Infect Dis 18:283–285

    CAS  PubMed  Google Scholar 

  31. Schuttrumpf S, Binder L, Hagemann T, Berkovic D, Trumper L, Bin C (2003) Procalcitonin: a useful discriminator between febrile condition of different origin in hemato-oncological patients? Ann Hematol 82:98–103

    CAS  PubMed  Google Scholar 

  32. Schwenger V, Sis J, Breitbart A, Andrassy K (1996) CRP levels in auto-immune disease can be specified by measurement of procalcitonin. Infection 24:434–436

    PubMed  Google Scholar 

  33. Urgate H, Silva E, Mercan D, Vincent JL (1999) Procalcitonin used as a marker of infection in the intensive care unit. Critical Care Med 27:452–453

    Google Scholar 

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Correspondence to Nicolas Penel.

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Penel, N., Fournier, C., Clisant, S. et al. Causes of fever and value of C-reactive protein and procalcitonin in differentiating infections from paraneoplastic fever.. Support Care Cancer 12, 593–598 (2004).

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