This document discusses fever of unknown origin (FUO), providing criteria for FUO, potential etiologies including infections, malignancies, and miscellaneous causes. It describes the characteristic history, physical exam findings, and key nonspecific test abnormalities that form the basis for a focused workup of FUO. Specific patient populations like those with HIV, solid organ transplants, or who have traveled are also discussed. The document concludes with considerations for therapy in FUO cases until a definite diagnosis can be made.

1. Fever of Unknown Origin
A clinical approach
-Sindhu Yarrabelli

2. Criteria
The definition of FUO derived by Petersdorf and Beeson in
1961 from a prospective analysis of 100 cases has long been
the clinical standard :
● Fever higher than 38.3ºC / 101 F on several occasions
● Duration of fever for at least three weeks
● Uncertain diagnosis after one week of study in the hospital

3. • Systemic rheumatic diseases
Giant cell arteritis
Polyarteritis nodosa
Still's disease
Etiology:
• Malignancy
Hepatocellular carcinoma or other tumors metastatic to the liver
Leukemia
Lymphoma
Renal cell carcinoma
• Miscellaneous
Factitious fever
Cirrhosis
Drug feverΔ
Cyclic Neutropenia

4. Infections
• Abscesses (especially
intra-abdominal)
• Tuberculosis
• Osteomyelitis
• Endocarditis
Culture-negative endocarditis
Cytomegalovirus
Pyelonephritis
ProstatitisGonococcal arthritis
Infectious mononeucleosis
Q fever*
Dental abscesses
Dengue
Chronic active hepatitis
Lyme disease*
Rheumatic fever
Sinusitis
Leptospirosis*
Zika virus*

5. Amebic liver abscess*
Anaplasmosis/ehrichiosis*
Babesiosis*
Brucellosis*
Castleman's disease
African tick bite fever*
Relapsing fever (Borrelia recurrentis)*
Toxoplasmosis
Typhoid fever*
Whipple's disease
Chikungunya*
Diskitis
Epididymitis
Fascioloiasis*
Filariasis*
Lassa fever*
Herpes simplex encephalitis
Kala azar (visceral
leishmaniasis)*
Kikuchi's disease
Pyometria

6. Epidemiology:
The percentage of patients with fever of unknown origin by cause during
four decades

7. Characteristic history (symptom)
+
physical examination findings (sign)
+
key nonspecific test abnormalities
Basis for a focused clue-directed fever of unknown
origin work-up.

8. • Travel
• Animal exposure
• Immunosuppression
• Drug and toxin history
• Localizing symptoms
• Surgical history, Blood transfusion
• Hallmark clinical features characteristic of each disorder
• Pattern of organ involvement
History

9. Physical Exam
• Eyes (Fundoscopy)
• Skin & LymphNodes
• Hepatomegaly & Splenomegaly
• Spinal tenderness
• Epididymoorchitis
• Morning temperature spikes
• Relative bradycardia
• Double quotidian fevers (2 fever spikes/day)
• Camel back fever curve (2 Fever peaks/week)
Fever pattern analysis

10. Nonspecific lab tests
HIV immuno assay
ESR, Rheumatoid Factor titres
Serum ferritin, ALP, LDH
Atypical lymphocytes
CBC with differential
Serum protein electrophoresis
Microscopic hematuria
Naprosyn test
IgM/IgG titres: Q fever, Brucella
Bartonella, Salmonella
EBV/CMV/HHV-8
PPD/T spot/Anergy panel
ANA titres
Heterophile antibody

11. Imaging CT/MRI abd /pelvis/chest
Nuclear scans[gallium indium scans]
Echo/TTE/TEE
PET-CT
Invasive tests
Lymph node biopsy
Bone marrow biopsy/culture
Epidydymal nodule biopsy
Ileal biopsy

12. FUO in HIV
Acute -fuo with mononucleosis like syndrome
Chronic- fuo as a manifestation of opportunistic infection / malignancy/drug fever
FUO in solid organ transplant Patients
Meningitis- Tb, crypto, endemic fungi
Focal brain lesion- Nocardia Toxo aspergillosis or lymphoma
Meningoencephalitis-CMV, VZV, west nile virus
Skin lesions- disseminated fungi (fusarium)

13. FUO in returning travellers
Milk- Brucellosis
Tick/louse borne relapsing fevers
Malaria
Viral Hep
Typhoid
Leptospirosis
Endemic mycosis
Rickettsial diseases
Amebic liver abscess
Schistosomiasis
AA trypanosomiasis
dengue, chickungunya
Yellow fever, West Nile,
Japanese enceph

14. Therapy in fever of unknown origin
• Until a definite fever-of-unknown origin diagnosis, antipyretic
or antimicrobial therapy should be avoided
• Emperic therapy in life threatening fUO