Fever of unknown origin is a challenging diagnostic problem and the aim of this research was to analyze trends in the distribution of its causative diseases. This retrospective study makes a comparison between two different clinical series of patients from two different periods: 227 from period 1 (1998–2002) and 602 from period 2 (2008–2012). There were fewer infections (31.72% vs.16.45%) and more miscellaneous causes (5.29% vs. 13.12%) in the period 2 series, whereas no significant differences in autoimmune diseases, malignancies and undiagnosed cases were found. Adult onset Still’s disease and lymphoma occupied the largest proportion in autoimmune diseases (75.00%) and malignancies (89.81%), respectively. Interestingly, the autoimmune diseases group, instead of infections, was found to be the leading category of the causative diseases in fever of unknown origin, which is contrary to previous reports. Further, adult onset Still’s disease and lymphoma were suggested to be valued more highly in view of the large and rising proportions found in this study. These trends could support the diagnosis and treatment of fever of unknown origin better in the future.
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Fever of unknown origin
Petersdorf RG, Beeson PB. Fever of unexplained origin: report on 100 cases. Medicine (Baltimore). 1961;40:1–30.
Durack DT, Street AC. Fever of unknown origin – reexamined and redefined. Curr Clin Top Infect Dis. 1991;11:35–51.
Knockaert DC, Vanderschueren S, Blockmans D. Fever of unknown origin in adults: 40 years on. J Intern Med. 2003;253:263–75.
Zenone T. Fever of unknown origin in adults: evaluation of 144 cases in a non-university hospital. Scand J Infect Dis. 2006;38:632–8.
Efstathiou SP, Pefanis AV, Tsiakou AG, Skeva II, Tsioulos DI, Achimastos AD, et al. Fever of unknown origin: discrimination between infectious and non-infectious causes. Eur J Intern Med. 2010;21:137–43.
Shi XC, Liu XQ, Zhou BT, Zhang LF, Ma XJ, Deng GH, et al. Major causes of fever of unknown origin at Peking Union Medical College Hospital in the past 26 years. Chin Med J (Engl). 2013;126:808–12.
Tan XY, He QY. Chinese literature review of etiology distribution of adult patients with fever of unknown origin from 1979 to 2012. Zhonghua Nei Ke Za Zhi. 2013;52:1013–7.
Bandyopadhyay D, Bandyopadhyay R, Paul R, Roy D. Etiological study of Fever of unknown origin in patients admitted to medicine ward of a teaching hospital of eastern India. J Glob Infect Dis. 2011;3:329–33.
Mete B, Vanli E, Yemisen M, Balkan II, Dagtekin H, Ozaras R, et al. The role of invasive and non-invasive procedures in diagnosing fever of unknown origin. Int J Med Sci. 2012;9:682–9.
Pedersen TI, Roed C, Knudsen LS, Loft A, Skinhoj P, Nielsen SD. Fever of unknown origin: a retrospective study of 52 cases with evaluation of the diagnostic utility of FDG-PET/CT. Scand J Infect Dis. 2012;44:18–23.
Naito T, Mizooka M, Mitsumoto F, Kanazawa K, Torikai K, Ohno S, et al. Diagnostic workup for fever of unknown origin: a multicenter collaborative retrospective study. BMJ Open. 2013;3:e003971.
Li Y. China’s misuse of antibiotics should be curbed. BMJ. 2014;348:g1083.
Petri M, Orbai AM, Alarcon GS, Gordon C, Merrill JT, Fortin PR, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012;64:2677–86.
Wouters JM, van der Veen J, van de Putte LB, de Rooij DJ. Adult onset Still’s disease and viral infections. Ann Rheum Dis. 1988;47:764–7.
Pouchot J, Sampalis JS, Beaudet F, Carette S, Decary F, Salusinsky-Sternbach M, et al. Adult Still’s disease: manifestations, disease course, and outcome in 62 patients. Medicine (Baltimore). 1991;70:118–36.
Sampalis JS, Medsger TA Jr., Fries JF, Yeadon C, Senecal JL, Myhal D, et al. Risk factors for adult Still’s disease. J Rheumatol. 1996;23:2049–54.
Ota T, Higashi S, Suzuki H, Eto S. Increased serum ferritin levels in adult Still’s disease. Lancet. 1987;1:562–3.
Akritidis N, Giannakakis I, Giouglis T. Ferritin levels and response to treatment in patients with Adult Still’s disease. J Rheumatol. 1996;23:201–2.
Fautrel B, Le Moel G, Saint-Marcoux B, Taupin P, Vignes S, Rozenberg S, et al. Diagnostic value of ferritin and glycosylated ferritin in adult onset Still’s disease. J Rheumatol. 2001;28:322–9.
Zeng T, Zou YQ, Wu MF, Yang CD. Clinical features and prognosis of adult-onset still’s disease: 61 cases from China. J Rheumatol. 2009;36:1026–31.
Efthimiou P, Paik PK, Bielory L. Diagnosis and management of adult onset Still’s disease. Ann Rheum Dis. 2006;65:564–72.
Yamaguchi M, Ohta A, Tsunematsu T, Kasukawa R, Mizushima Y, Kashiwagi H, et al. Preliminary criteria for classification of adult Still’s disease. J Rheumatol. 1992;19:424–30.
Masson C, Le Loet X, Liote F, Dubost JJ, Boissier MC, Perroux-Goumy L, et al. Comparative study of 6 types of criteria in adult Still’s disease. J Rheumatol. 1996;23:495–7.
Gerfaud-Valentin M, Maucort-Boulch D, Hot A, Iwaz J, Ninet J, Durieu I, et al. Adult-onset still disease: manifestations, treatment, outcome, and prognostic factors in 57 patients. Medicine (Baltimore). 2014;93:91–9.
The International Non-Hodgkin’s Lymphoma Prognostic Factors Project. A predictive model for aggressive non-Hodgkin’s lymphoma. N Engl J Med. 1993;329:987–94.
Cunha BA. Fever of unknown origin: focused diagnostic approach based on clinical clues from the history, physical examination, and laboratory tests. Infect Dis Clin North Am. 2007;21:1137–87.
Kim YJ, Kim SI, Hong KW, Kang MW. Diagnostic value of 18F-FDG PET/CT in patients with fever of unknown origin. Intern Med J. 2012;42:834–7.
Kouijzer IJ, Bleeker-Rovers CP, Oyen WJ. FDG-PET in fever of unknown origin. Semin Nucl Med. 2013;43:333–9.
Becerra Nakayo EM, Garcia Vicente AM, Soriano Castrejon AM, Mendoza Narvaez JA, Talavera Rubio MP, Poblete Garcia VM, et al. Analysis of cost-effectiveness in the diagnosis of fever of unknown origin and the role of (18)F-FDG PET-CT: a proposal of diagnostic algorithm. Rev Esp Med Nucl Imagen Mol. 2012;31:178–86.
Mourad O, Palda V, Detsky AS. A comprehensive evidence-based approach to fever of unknown origin. Arch Intern Med. 2003;163:545–51.
Horowitz HW. Fever of unknown origin or fever of too many origins? N Engl J Med. 2013;368:197–9.
This work was supported by research grants from the Technology Major Project no. 2013ZX10002005.
Conflict of interest
J. Shang, L. Yan, L. Du, L. Liang, Q. Zhou, T Liang, L. Bai, and H. Tang declare that they have no competing interests.
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Shang, J., Yan, L., Du, L. et al. Recent trends in the distribution of causative diseases of fever of unknown origin. Wien Klin Wochenschr 129, 201–207 (2017). https://doi.org/10.1007/s00508-016-1159-6
- Fever of unknown origin
- Autoimmune diseases
- Adult-onset Still’s disease