Skip to main content

Advertisement

SpringerLink
Log in

Lessons learned from splenic infarcts with fever of unknown origin (FUO): culture-negative endocarditis (CNE) or malignancy?

  • Review
  • Published:
European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

Abstract

Culture negative endocarditis (CNE) is a common concern in patients with fever, heart murmur, cardiac vegetation, and negative blood cultures. The diagnosis of CNE is not based only on negative blood cultures and a cardiac vegetation. The clinical definition of CNE is based on negative blood cultures plus the findings of culture positive infective endocarditis (IE), e.g., fever, cardiac vegetation, splenomegaly, peripheral manifestations. Because embolic splenic infarcts may occur with culture positive IE, some may assume that splenic infarcts are a sign of CNE. Previously, CNE was due to fastidious and non-culturable organisms. With current diagnostic methods, fastidious organisms grow in 2–3 days. Therefore, fastidious IE are a subset of culture positive IE, but do not represent true CNE. We describe a case of an elderly female who presented with a fever of unknown origin (FUO) and multiple splenic infarcts thought by some to represent CNE. An extensive workup for CNE pathogens was negative. The final cause of her splenic infarcts was a diffuse large B-cell lymphoma (DLBCL). Review of the literature, as well as this case, confirms that splenic infarcts are not a feature of CNE. In patients with fever, splenic infarcts, and negative blood cultures, physicians should search for an alternate explanation rather than CNE, e.g., malignancy and hypercoaguable state (lupus anticoagulant).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Peterdorf RG, Beeson PB (1961) Fever of unexplained origin: report on 100 cases. Medicine (Baltimore) 40:1–3

    Article  Google Scholar 

  2. Peterdorf RG (1992) Fever of unknown origin: an old friend revisited. Arch Intern Med 152:21–22

    Article  Google Scholar 

  3. Murray HW (ed) (1983) FUO: fever of undetermined origin. Futura Publishing, Mount Kisko

    Google Scholar 

  4. Cunha BA (ed) (2007) Fever of unknown origin. Informa, New York

    Google Scholar 

  5. Brusch JL, Weinstein L (1988) Fever of unknown origin. Med Clin N Am 72:1247–1261

    Article  CAS  PubMed  Google Scholar 

  6. Cunha BA (2007) Fever of unknown origin: focused diagnostic approach based on clinical clues from the history, physical examination, and laboratory tests. Infect Dis Clin N Am 21:1137–1187

    Article  Google Scholar 

  7. Cunha CB (2017) Diagnositc tests in infectious diseases. In: Cunha CB, Cunha BA (eds) Antibiotic Essentials, 15th edn. JayPee Medical Publishers, New Delhi, pp 1137–1187

    Google Scholar 

  8. Cunha BA (2004) Fever of unknown origin. In: Gorbach SL, Bartlett JG, Blacklow NR (eds) Infectious diseases, 3rd edn. Lippincott Williams & Wilkins, New York, pp 1568–1577

    Google Scholar 

  9. Cunha CB, Cunha BA (2015) Fever of unknown origin. In: Schlossberg D (ed) Clinical infectious disease. Cambridge University Press, Cambridge, pp 2–12

    Chapter  Google Scholar 

  10. Cunha BA (2004) Fever in malignant disorders. Infect Dis Pract 26:335–336

    Google Scholar 

  11. Luft FC, Rissing JP, White A, Brooks GF (1976) Infections or neoplasm as causes of prolonged fever in cancer patients. Am J Med Sci 272:65–74

    Article  CAS  PubMed  Google Scholar 

  12. Meytes D, Ballin A (1991) Unexplained fever in hematologic disorders: malignant hematologic disorders. In: Isaac B, Kernbaum S, Burke M (eds) Unexplained fever. CRC Press, Boca Raton, pp 209–224

    Google Scholar 

  13. Wang C, Armstrong D (1983) Neoplastic disease. In: Murray HW (ed) FUO: fever of undetermined origin. Futura, Mount Kisko, pp 39–46

    Google Scholar 

  14. Roca CV, Rodriguez SH (2007) Malignant lymphomas presenting as fever of unknown origin. An Med Interna 24:531–534

    Google Scholar 

  15. Weinstein L, Brusch JL (eds) (1996) Infective endocarditis. Oxford University Press, New York

    Google Scholar 

  16. McDermott BP, Cunha BA, Choi D, Cohen J, Hage J (2011) Transthoracic echocardiography (TTE): sufficiently sensitive screening test for native vale infection endocarditis (IE). Heart Lung 40:358–360

    Article  PubMed  Google Scholar 

  17. Rubenson DS, Tucker CR, Stinson EG (1981) The use of echocardiography in diagnosing culture negative endocarditis. Circulation 64:641–646

    Article  CAS  PubMed  Google Scholar 

  18. Cunha BA (2007) The mimics of endocarditis. In: Brusch J (ed) Infectious endocarditis. Informa, NY, pp 345–353

    Google Scholar 

  19. Van Scoy RE (1982) Culture negative endocarditis. Mayo Clin Proc 5:149–154

    Google Scholar 

  20. Brusch J (2007) Organisms of blood culture-negative endocarditis. In: Brusch J (ed) Infectious endocarditis. Informa, NY, pp 73–99

    Google Scholar 

  21. Raoult D, Casalta JP, Richet H, Khan M, Bernit E, Rovery C et al (2005) Contribution of systemic serological testing in diagnosis of infective endocarditis. J Clin Microbiol 43:5238–5242

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Houpikian P, Raoult D (2005) Blood culture negative endocarditis in a reference center. Medicine 84:162

    Article  PubMed  Google Scholar 

  23. Lamas CC, Eykyn SJ (2003) Blood culture negative endocarditis: analysis of 63 cases presenting over 25 years. Heart 89:258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Fournier PE, Thuny F, Richet H, Lepidi H, Casalta JP, Arzouni JP et al (2010) Comprehensive diagnostic strategy for blood culture negative endocarditis: a prospective study of 819 new cases. Clin Infect Dis 51:131–140

    Article  CAS  PubMed  Google Scholar 

  25. Pesanti EL, Smith IM (1979) Infective endocarditis with negative blood cultures: an analysis of 52 cases. Am J Med 66:43–50

    Article  CAS  PubMed  Google Scholar 

  26. Cannaday PB, Sanford JP (1976) Negative blood cultures in infective endocarditis: a review. South Med J 69:1420–1424

    Article  Google Scholar 

  27. Brouqui P, Raoult D (2001) Endocarditis due to rare and fastidious bacteria. Clin Microbiol Rev 14:177–207

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Brensilver HL, Kaplan MM (1975) Significance of elevated liver alkaline phosphatase in serum. Gastroenterology 68:1556–1562

    CAS  PubMed  Google Scholar 

  29. Cunha BA (2007) Fever of unknown origin (FUO). Diagnostic serum ferritin levels. Scand J Infect Dis 39:651–652

    Article  PubMed  Google Scholar 

  30. Cunha BA (2004) Diagnostic significance of nonspecific laboratory tests in infectious diseases. In: Bartlett JG, Blacklow NR (eds) Infectious diseases, 3rd edn. Lippincott Williams, Baltimore, pp 158–166

    Google Scholar 

  31. Baldridge CW, Awe CD (1938) Lymphoma: a study of one hundred and fifty cases. Arch Intern Med 45:161–190

    Article  Google Scholar 

  32. Hsi ED, Gascoyne RD, Goldblum RD (2007) Diffuse aggressive B-cell lymphomas. In: His ED, Goldblum RD (eds) Hematopathology. Churchill Livingston, Philadelphia, pp 259–282

    Google Scholar 

  33. Jaroch MT, Broughan TA, Hermann RE (1986) The natural history of splenic infarction. Surgery 100:743–750

    CAS  PubMed  Google Scholar 

  34. Goerg C, Schwerk WB (1990) Splenic infarction: sonographic patterns, diagnosis, follow up and complications. Radiology 174:803–807

    Article  CAS  PubMed  Google Scholar 

  35. Nores M, Phillips EH, Morgenstern L, Hiatt JR (1998) The clinical spectrum of splenic infarction. Am Surg 64:182–188

    CAS  PubMed  Google Scholar 

  36. Antopolsky M, Hiler N, Salameh S, Godstein S, Stalnikowicz R (2009) Splenic infarction: 10 years of experience. Am J Emerg Med 27:262–265

    Article  PubMed  Google Scholar 

  37. Cunha BA, Sivarajah T, Jimada I (2017) Sarcoidosis with fever and a splenic infarct due to CMV or lymphoma? Heart Lung 46:394–396

    Article  PubMed  Google Scholar 

  38. Cunha BA, Petelin A (2013) Fever of unknown origin (FUO) due to large B-cell lymphoma: the diagnostic significance of highly elevated alkaline phosphatase and serum ferritin levels. Heart Lung 42:67–71

    Article  PubMed  Google Scholar 

  39. Iioka F, Honjo G, Misaki T et al (2016) A unique subtype of duffuse large B-cell lymphoma primarily involving the bone marrow, spleen and liver defined by fluorodeoxyglucose-positron emission tomography combined with computed tomography. Leuk Lymphoma 57:2593–2602

    Article  CAS  PubMed  Google Scholar 

  40. Cunha BA (2007) Fever of unknown origin: clinical overview of classic and current concepts. Infect Dis Clin N Am 21:867–915

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Infectious Disease Division, NYU Winthrop Hospital, 222 Station Plaza North (Suite #432), Mineola, NY, 11501, USA

    Burke A. Cunha, Bertamaria Dieguez & Alena Varantsova

  2. School of Medicine, State University of New York, Stony Brook, NY, USA

    Burke A. Cunha, Bertamaria Dieguez & Alena Varantsova

Authors
  1. Burke A. Cunha
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bertamaria Dieguez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alena Varantsova
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Burke A. Cunha.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

N/a

Informed consent

N/a

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cunha, B.A., Dieguez, B. & Varantsova, A. Lessons learned from splenic infarcts with fever of unknown origin (FUO): culture-negative endocarditis (CNE) or malignancy?. Eur J Clin Microbiol Infect Dis 37, 995–999 (2018). https://doi.org/10.1007/s10096-018-3200-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-018-3200-3

Keywords

Search

Navigation