View source for Fever of unknown origin

==Background==

*Typically defined as a persistent fever that remains undiagnosed despite an extensive initial workup
*Causes have changed over the decades as diagnostic tools have improved

===Definitions===
{| class="wikitable"
!Type
!Definition
|-
|Classic
|Temperatures >38.3ºC without diagnosis despite 3 weeks of outpatient investigations over 3 visits, or 1 week of intensive outpatient investigation, or 3 days of inpatient investigation
|-
|Nosocomial
|Temperatures >38.3ºC without diagnosis in a hospitalized acute-care patient, where infection was not community-acquired, despite 3 days of investigations including preliminary results of blood cultures at 48 hours
|-
|Neutropenic
|Temperatures >38.3ºC without diagnosis in patients with neutrophils <500/μL or expected to fall to that level in 1-2 days, despite initial investigations including preliminary results of blood cultures at 48 hours
|-
|[[HIV]]-associated
|Temperatures >38.3ºC without diagnosis over 4 weeks (outpatient) or 3 days (inpatient) in patients with HIV, despite initial investigations including preliminary results of blood cultures at 48 hours
|}

==Differential Diagnosis==

*'''Infectious''' (16 to 52%)
**More common: [[tuberculosis]] (especially extrapulmonary disease), [[culture-negative endocarditis]], [[Epstein-Barr virus]], [[cytomegalovirus]]
**More common, in recent travelers: [[malaria]] and [[dengue]]
**Less common: [[bartonellosis]], [[brucellosis]], occult [[abscess]], [[salmonellosis]], [[urinary tract infection]], [[acute HIV]], [[hepatitis A]], [[hepatitis B]], [[hepatitis E]], [[roseolavirus]], [[HHV-7]], [[osteomyelitis]], [[septic arthritis]]
**Less common, in recent travelers: [[rickettsioses]], [[leptospirosis]], [[schistosomiasis]], [[gnathostomiasis]], [[cysticercosis]], [[enteric fever]]
*'''Neoplastic''' (7 to 35%)
**More common: [[lymphoma]], [[leukemia]], [[solid organ tumour]] (especially [[renal cell carcinoma]] and [[melanoma]])
**Less common: [[myelodysplastic syndrome]], [[colonic adenocarcinoma]], [[multiple myeloma]], [[gastric carcinoma]], [[mesothelioma]], [[Castleman disease]]
*'''Inflammatory''' (11 to 34%)
**More common: [[adult-onset Still disease]], [[systemic lupus erythematosus]], [[polymyalgia rheumatica]], [[temporal arteritis]], [[inflammatory bowel disease]]
**Less common: [[rheumatoid arthritis]], [[polyarteritis nodosa]], [[sarcoidosis]], [[granulomatosis with polyangiitis]], [[Kawasaki syndrome]]
*'''Other''' (2 to 20%)
**More common: [[drug fever]], [[chronic pulmonary embolism]], [[hyperthyroidism]], [[hematoma]]
**Less common: [[subacute thyroiditis]], [[hypoadrenalism]], [[necrotizing lymphadenitis]], [[periodic fever syndromes]], [[hemophagocytic lymphohistiocytosis]], [[factitious fever]]
*'''Undiagnosed''' (7 to 32%)

== Investigations ==

* ESR or CRP, LDH, CK, ANA, RF, SPEP
* Blood cultures x3
* HIV serology
* Heterophile antibody test (in children or young adults)
* TST or IGRA
* CT of the abdomen and chest

==Further Reading==

*Fever and Fever of Unknown Origin: Review, Recent Advances, and Lingering Dogma. ''Open Forum Infect Dis''. 2020. doi: [https://doi.org/10.1093/ofid/ofaa132 10.1093/ofid/ofaa132]

[[Category::Fever syndromes]]