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Category-based definitions of FUO

Category-based definitions of FUO
Category Commonly used definition
Classic FUO Temperature >38.3°C (100.9°F) recorded on several occasions for >3 weeks, despite 3 outpatient clinic evaluations, 1 week of intensive outpatient investigation, or 3 days of hospital-based evaluation.*
Health care-associated FUO
  • ICU patient
 Temperature >38.3°C (100.9°F) recorded on several occasions in an ICU patient despite ≥3 days of investigations. Fever must not have been present or incubating on admission.
  • Non-ICU patient
 Same definition as for ICU patient, except patient is hospitalized but not critically ill.
  • Post-operative patient
 Same definition as for ICU patient, except fever is usually defined as ≥38.0°C (100.4°F).
FUO in immunocompromised patients
  • Neutropenic patients
 Temperature ≥38.3°C (100.9°F) or ≥38.0°C (100.4°F) sustained over a one-hour period, recorded on several occasions over at least 3 days, despite appropriate antimicrobial therapy. Neutropenia is defined as <500 neutrophils/microL or impending fall to that level within 48 hours.
  • Patients with HIV and CD4 count <200 cells/microL
 Temperature ≥38.3°C (100.9°F) recorded on several occasions for >3 weeks for outpatient or >3 days for inpatient despite appropriate evaluation.
Travel-associated FUO Temperature >38.3°C (100.9°F) recorded on several occasions for >3 weeks, despite 3 outpatient clinic evaluations, 1 week of intensive outpatient investigation, or 3 days of hospital-based evaluation, in a patient who travelled to another country, typically within the prior 12 months.
FUO definitions vary. An overarching definition of FUO is fever in the absence of an identifiable cause despite reasonable evaluation in either the inpatient or outpatient setting; the fever must persist longer than typical or suspected self-limiting conditions, such as common viral illnesses. A specific temperature threshold to define a fever is debatable as well; most studies define fever as a temperature >38.3°C (100.9°F), although definitions range from 38.0°C (100.4°F) to 38.5°C (101.3°F).

FUO: fever of unknown origin.

* Because peak normal temperature in well individuals is 38.0°C, some experts have proposed a cut-off temperature for classic FUO of >38.0°C (100.4°F) instead of >38.3°C (100.9°F).[1]

¶ Formal definitions for FUO have not been defined for immunocompromising conditions other than neutropenia and HIV.
Reference:
  1. Wright WF, Mulders-Manders CM, Auwaerter PG, et al. Fever of unknown origin (FUO) – A call for new research standards and updated clinical management. Am J Med 2022; 135:173.

Adapted from:

  1. Wright W, Mackowiak P. Fever of unknown origin. In: Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 8th ed, Bennett J, Dolin R, Blaser M (Eds), Elsevier Saunders 2015. p. 721.
  2. Haidar G, Singh N. Fever of Unknown Origin. N Engl J Med. 2022; 386:463.
  3. Wright WF, Auwaerter PG. Fever and fever of unknown origin: Review, recent advances, and lingering dogma. Open Forum Infect Dis 2020; 7:ofaa132.
  4. Durack DT, Street AC. Fever of unknown origin – reexamined and redefined. Curr Clin Top Infect Dis 1991; 11:35.
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