A pyrexia of unknown origin, commonly shortened to PUO and also known as a fever of unknown origin (FUO), was originally defined in 1961 as the condition in which the core body temperature is >38.3 oC for a period of three weeks or more, with no diagnosis reached after one week of inpatient investigation 1. Setting the period at ≥3 weeks was not arbitrary, but was felt likely to exclude self-limited viral infections, which usually resolve in under 3 weeks 5.
In modern practice the term is often used more loosely by clinicians for any case in which a patient presents with a persistent fever without clear cause after a set of reasonable initial investigations. A typical request for a CT chest abdomen and pelvis for such a case may follow along the lines of "PUO, ? source of infection".
More recently the term inflammation of unknown origin has been coined for cases of unexplained chronic inflammation without fever. Unsurprisingly there is a certain degree of overlap between the causes of pyrexia/fever of unknown origin and inflammation of unknown origin 5.
Of course the possible causes of pyrexia are broad and not just restricted to infections, with both neoplasms and inflammatory disorders figuring heavily in the etiologies.
In one published prospective series from 1997, 26% had infections, 13% had neoplasms, and 24% had non-infectious inflammatory diseases. In 30% patients no cause could be found despite an extensive investigative work-up 2.
A series from India published in 2001 showed that infection featured more prominently than in Western series with tuberculosis, bacterial endocarditis and abscesses all accounting for a significant share of cases 3. However non-infective causes were broad and varied including cancers and inflammatory disorders. Malignancies were both hematological (Hodgkin and non-Hodgkin lymphoma) and visceral (colon cancer, ovarian carcinoma and bronchogenic carcinoma). Non-infectious inflammatory diseases included lupus, Takayasu arteritis, mixed connective tissue disease, ankylosing spondylitis and polyarteritis nodosa. Other causes in this series, each diagnosed in a single patient, included sarcoidosis, granulomatous hepatitis, autoimmune hepatitis, atrial myxoma and a drug fever 3.
Emerging evidence backs up the use of the PET-CT in the investigation of pyrexia/fever of unknown origin. In a recent prospective study, it was found that PET-CT was diagnostic in greater than half of all cases 4.
- 1. Petersdorf RG, Beeson PB. Fever of unexplained origin: report on 100 cases. Medicine. 40: 1-30. Pubmed
- 2. de Kleijn EM, Vandenbroucke JP, van der Meer JW. Fever of unknown origin (FUO). I A. prospective multicenter study of 167 patients with FUO, using fixed epidemiologic entry criteria. The Netherlands FUO Study Group. Medicine. 76 (6): 392-400. Pubmed
- 3. Kejariwal D, Sarkar N, Chakraborti SK, Agarwal V, Roy S. Pyrexia of unknown origin: a prospective study of 100 cases. Journal of postgraduate medicine. 47 (2): 104-7. Pubmed
- 4. Schönau V, Vogel K, Englbrecht M, Wacker J, Schmidt D, Manger B, Kuwert T, Schett G. The value of F-FDG-PET/CT in identifying the cause of fever of unknown origin (FUO) and inflammation of unknown origin (IUO): data from a prospective study. (2018) Annals of the rheumatic diseases. 77 (1): 70-77. doi:10.1136/annrheumdis-2017-211687 - Pubmed
- 5. Balink H, Verberne HJ, Bennink RJ, van Eck-Smit BL. A Rationale for the Use of F18-FDG PET/CT in Fever and Inflammation of Unknown Origin. (2012) International journal of molecular imaging. 2012: 165080. doi:10.1155/2012/165080 - Pubmed