Int J Med Sci 2012; 9(8):682-689. doi:10.7150/ijms.4591 This issue

Research Paper

The Role of Invasive and Non-Invasive Procedures in Diagnosing Fever of Unknown Origin

Bilgul Mete, Ersin Vanli, Mucahit Yemisen, Ilker Inanc Balkan, Hilal Dagtekin, Resat Ozaras, Nese Saltoglu, Ali Mert, Recep Ozturk, Fehmi Tabak

Istanbul University Cerrahpasa Medical Faculty, Department of Infectious Diseases and Clinical Microbiology, Istanbul/Turkey

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See for full terms and conditions.
Mete B, Vanli E, Yemisen M, Balkan II, Dagtekin H, Ozaras R, Saltoglu N, Mert A, Ozturk R, Tabak F. The Role of Invasive and Non-Invasive Procedures in Diagnosing Fever of Unknown Origin. Int J Med Sci 2012; 9(8):682-689. doi:10.7150/ijms.4591. Available from

File import instruction


Background: The etiology of fever of unknown origin has changed because of the recent advances in and widespread use of invasive and non-invasive diagnostic tools. However, undiagnosed patients still constitute a significant number.

Objective: To determine the etiological distribution and role of non-invasive and invasive diagnostic tools in the diagnosis of fever of unknown origin.

Materials & Methods: One hundred patients who were hospitalized between June 2001 and 2009 with a fever of unknown origin were included in this study. Clinical and laboratory data were collected from the patients' medical records retrospectively.

Results: Fifty three percent of the patients were male, with a mean age of 45 years. The etiology of fever was determined to be infectious diseases in 26, collagen vascular diseases in 38, neoplastic diseases in 14, miscellaneous in 2 and undiagnosed in 20 patients. When the etiologic distribution was analyzed over time, it was noted that the rate of infectious diseases decreased, whereas the rate of rheumatological and undiagnosed diseases relatively increased because of the advances in imaging and microbiological studies. Seventy patients had a definitive diagnosis, whereas 10 patients had a possible diagnosis. The diagnoses were established based on clinical features and non-invasive tests for 61% of the patients and diagnostic benefit was obtained for 49% of the patients undergoing invasive tests. Biopsy procedures contributed a rate of 42% to diagnoses in patients who received biopsies.

Conclusion: Clinical features (such as detailed medical history-taking and physical examination) may contribute to diagnoses, particularly in cases of collagen vascular diseases. Imaging studies exhibit certain pathologies that guide invasive studies. Biopsy procedures contribute greatly to diagnoses, particularly for malignancies and infectious diseases that are not diagnosed by non-invasive procedures.

Keywords: fever of unknown origin, invasive investigations, non-invasive techniques