Intended for healthcare professionals

Clinical Review

Investigating and managing pyrexia of unknown origin in adults

BMJ 2010; 341 doi: (Published 15 October 2010) Cite this as: BMJ 2010;341:c5470
  1. George M Varghese, professor1,
  2. Paul Trowbridge, resident2,
  3. Tom Doherty, consultant physician3
  1. 1Department of Medicine and Infectious Diseases, Christian Medical College, Vellore, India
  2. 2Department of Internal Medicine, Rhode Island Hospital/Brown University, Providence, USA
  3. 3Hospital for Tropical Diseases, London, UK
  1. Correspondence to: G M Varghese georgemvarghese{at}
  • Accepted 21 September 2010

Summary points

  • Classic adult pyrexia of unknown origin is fever of 38.3°C or greater for at least 3 weeks with no identified cause after three days of hospital evaluation or three outpatient visits

  • Common causes are infections, neoplasms, and connective tissue disorders

  • A thorough history and physical examination, along with basic investigations will usually provide clues to a possible diagnosis that can guide the choice of further investigations

  • If the initial evaluation provides no diagnostic clues, further investigations including imaging studies and serological tests may be indicated

  • A watch and wait approach is acceptable in a clinically stable patient for whom no diagnosis can be made after extensive investigation, and the prognosis is likely to be good

  • Empirical antibiotics are warranted only for individuals who are clinically unstable or neutropenic. In stable patients empirical treatment is discouraged, although NSAIDs may be used after investigations are complete. Empirical corticosteroid therapy is discouraged

Few clinical problems generate such a wide differential diagnosis as pyrexia (fever) of unknown origin. The initial definition proposed by Petersdorf and Beeson in 1961,1 later revised, is “a fever of 38.3°C (101°F) or more lasting for at least three weeks for which no cause can be identified after three days of investigation in hospital or after three or more outpatient visits.”2 3 4 Essentially the term refers to a prolonged febrile illness without an obvious cause despite reasonable evaluation and diagnostic testing. A fever that is not self limiting for which no cause can be found can become a source of frustration for both patient and doctor. There is little consensus on how such patients should be investigated, although recent prospective studies have evaluated diagnostic protocols to suggest approaches to investigation.3 5 6 We discuss evidence from epidemiological and diagnostic studies and suggest an approach to investigating …

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