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Definition
Fever > 38.3 on several occasions Fever lasting more than 3 weeks No diagnosis despite 1 week of inpatient workup
Potential Etiologies
Based on patient population Classical Immunodeficient (Neutropenic) Nosocomial HIV related
Classic FUO
Fever > 38.3 Duration greater than 3 weeks Evaluation for 3 weeks as an outpatient or 3 days in hospital
Classic FUO
Infection Malignancy Collagen vascular diseases
Nosocomial FUO
Fever > 38.3 Patient hospitalized > 24 hours, but no fever on admission Evaluation for at least 3 days
Nosocomial FUO
Clostridium difficile Drug induced Pulmonary embolism Septic thrombophlebitis Sinusitis
Neutropenic FUO
Fever > 38.3 ANC 500 or less Evaluation for at least 3 days
Neutropenic FUO
Opportunistic bacterial infections Herpes Virus Aspergillosis Candidiasis
HIV FUO
Fever > 38.3 Duration > 4 weeks (outpatient) or > 3 days (inpatient) HIV infection confirmed
HIV FUO
CMV MAC PCP Drug induced Kaposis Sarcoma Lymphoma
Infections
Tuberculosis (especially extrapulmonary) Abdominal abscesses Pelvic abscesses Dental abscesses Endocarditis Osteomyelitis Sinusitis Cytomegalovirus Epstein-Barr virus Human immunodeficiency virus Lyme disease Prostatitis Sinusitis
Infections
As duration of fever increases, infectious etiology decreases Malignancy and factitious fevers are more common in patients with prolonged FUO.
Malignancies
Chronic leukemia Lymphoma Metastatic cancers Renal cell carcinoma Colon carcinoma Hepatoma Myelodysplastic syndromes Pancreatic carcinoma Sarcomas
Autoimmune
Adult Still's disease Polymyalgia rheumatica Temporal arteritis Rheumatoid arthritis Rheumatoid fever Inflammatory bowel disease Reiter's syndrome Systemic lupus erythematosus Vasculitides
Miscellaneous
Drug-induced fever Complications from cirrhosis Factitious fever Hepatitis (alcoholic, granulomatous, or lupoid) Deep venous thrombosis Sarcoidosis
Diagnosis
Failure to reach a diagnosis is not uncommon 20% of cases remain undiagnosed Even if extensive investigation does not identify a cause, these patients still have favorable outcomes.
Diagnosis
Comprehensive History Physical Exam
Laboratory Data
History
Recent travel Exposure to pets and other animals Sexual history Work environment Contact with other people with similar symptoms Family history Past medical history list of medications
Include OTC
Physical Exam
Skin Mucus membranes Lymphadenopathy Organomegaly
Diagnosis
A cost-effective individualized approach is essential in the evaluation of these patients to prevent performing inappropriate tests.
Diagnostic Testing
CBC LFTs ESR Urinalysis Blood cultures Further testing should be based on abnormalities in the initial workup
Diagnosis
PPD testing is inexpensive screening tool that should be used on all FUO patients that do not have a known positive reaction
Diagnosis
If initial testing is inconclusive- more specific testing should be performed based on clinical suspicion Serologies CT Ultrasounds MRI Nuclear Medicine Scans
Chest radiograph
Gallium 67 scan
Indium-labeled leukocytes
Technetium Tc 99m
MRI of brain
Acute infection and inflammation of bones and soft tissue Malignancy, autoimmune conditions Malignancy, inflammation Bacterial endocarditis Venous thrombosis
PET scan
Diagnosis
More invasive testing, such as LP or biopsy of bone marrow, liver, or lymph nodes, should be performed only when clinical suspicion shows that these tests are indicated or when the source of the fever remains unidentified after extensive evaluation. When the definitive diagnosis remains elusive and the complexity of the case increases, an infectious disease, rheumatology, or oncology consultation may be helpful.