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FUO
I.
Types
A.
Classic Fever of Unknown Origin
(1) Daily or Intermittent Fever >= 38.3 C (101 F)
(2) Duration for 3 consecutive weeks
(3) No source by clinical evaluation
a. Hospital evaluation for 3 days or
b. Intensive outpatient evaluation for 7 days or
c. Three outpatient visits
B.
Nosocomial Fever of Unknown Origin
C.
D.
II.
(1) Daily or Intermittent Fever >= 38.3 C (101 F)
(2) Hospitalized >1 day without fever on admission
(3) Fever evaluation of 3 days of more
Immune-Deficient Fever of Unknown Origin
(1) Daily or Intermittent Fever >= 38.3 C (101 F)
(2) Neutrophil Count <500 per mm3
(3) Fever evaluation of 3 days of more
HIV-Associated Fever of Unknown Origin
(1) Daily or Intermittent Fever >= 38.3 C (101 F)
(2) Outpatient fever >4 weeks or
(3) Inpatient fever >3 days
Causes
A.
Fever of Unknown Origin Causes
(1) Infections
a. Viral Syndrome
1. Cytomegalovirus
2. Epstein-Barr Virus (Mononucleosis)
3. HIV Infection
b. Lyme Disease
c. Pyelonephritis or Urinary Tract Infection
d. Meningitis
e. Pneumonia
f. Septicemia
g. Acute Sinusitis
h. Malaria
i. Osteomyelitis
j. Typhoid Fever or Enteric Fever
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k. Subacute Bacterial Endocarditis (SBE)
l. Tuberculosis
m. Liver or biliary Infection
n. Abdominal or Pelvic Abscess
o. Dental Abscess
p. Psittacosis
q. Brucellosis
r. Tonsillitis or Peritonsillar Abscess
s. Herpes Simplex Virus
t. Streptococcosis
u. Gonococcal Arthritis
v. Prostatitis
(2) Neoplastic Disease
a. Leukemia
b. Lymphoma
c. Sarcoma
d. Carcinomatosis
e. Renal cell carcinoma
f. Colon Cancer
g. Pancreatic carcinoma
h. Hepatoma
i. Metastatic cancer
(3) Autoimmune Disease
a. Juvenile Rheumatoid Arthritis (evanescent rash)
b. Henoch-Schonlein Purpura
c. Systemic Lupus Erythematosus
d. Rheumatic Fever (Migratory Polyarthritis)
e. Polymyalgia Rheumatica
d. Temporal Arteritis
e. Inflammatory Bowel Disease
f. Reiter's Syndrome
(4) Heritable Disease Causes
a. Fabry's Disease
b. Familial Mediterranean fever
c. Lamellar Ichthyosis
d. Nephrogenic Diabetes Insipidus
e. Anhydrotic ectodermal dysplasia
f. Familial Dysautonomia
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(5) Granulomatous Disease
a. Sarcoidosis
b. Granulomatous Hepatitis
c. Inflammatory Bowel Disease
(6) Miscellaneous
a. Factitious Fever (Munchausen by proxy)
b. Thyroiditis
c. Neurogenic Fever
d. Milk Allergy
e. Behcet's Syndrome
f. Anicteric Hepatitis
B.
g. Pulmonary Embolism
h. Deep Vein Thrombosis
Fever of Unknown Origin Causes by Age
(1) Causes: Age <6 years old
a. Infections (65%)
b. Neoplastic Disease (8%)
c. Autoimmune Disease (8%)
d. Miscellaneous (13%)
e. No Diagnosis (6%)
(2) Causes: Age 6 to 14 years old
a. Infections (38%)
b. Neoplastic Disease (4%)
c. Autoimmune Disease (23%)
d. Miscellaneous (17%)
e. No Diagnosis (19%)
(3) Causes: Age >14 years old
a. Infections (36%)
b. Neoplastic Disease (19%)
c. Autoimmune Disease (13%)
d. Miscellaneous (25%)
e. No Diagnosis (7%)
(4) Causes: Age >65 years old
a. Connective tissue disease (30%)
1. Temporal Arteritis
2. Polymyalgia Rheumatica
b. Infection (25%)
c. Cancer (12%)
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d. No Diagnosis (8%)
C.
Drug-Induced Fever
(1) Causes: Antibiotic Induced Fever
a. Erythromycin
b. Isoniazid
c. Penicillin
d. Nitrofurantoin
e. Procainamide
f. Quinidine
(2) Causes: Cardiovascular Medication Induced Fever
a. Atropine
b. Captopril
c. Clofibrate
d. Hydralazine
e. Hydrochlorothiazide
f. Methyldopa
g. Nifedipine
(3) Causes: Miscellaneous Medications Inducing Fever
a. Allopurinol
b. Antihistamines
c. Aspirin
d. Cimetidine
e. Heparin
f. Meperidine
g. Phenytoin
III.
History
A.
History: Fever
(1) Thermometer used and by what route?
(2) What was peak temperature?
(3) Did fever occur at predictable time of day?
B.
(4) Did fever occur daily, or intervening afebrile days?
(5) What was response to antipyretics?
History: Systemic Symptoms
(1) Weight loss
(2) Decreased appetite
(3) Decreased activity
(4) Onset of symptoms (Do symptoms precede fever?)
(5) Rash
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(6) Arthralgia
C.
D.
History: Localized Symptoms
(1) Headache
(2) Personality change
(3) Cough
(4) Abdominal pain
(5) Urinary Symptoms
(6) Bone pain
a. Local pain in Osteomyelitis
b. Multifocal pain in malignancy
History: Travel history and Exposures
(1) Travel outside Taiwan (Vaccines or prophylaxis?)
a. Tuberculosis
b. Malaria
c. Hepatitis
d. Salmonellosis
e. Brucellosis,
f. Leptospirosis
g. Various mycoses and parasites
(2) Camping or travel in wooded areas (Tick bites)
a. Rocky Mountain Spotted Fever
b. Lyme Disease
c. Relapsing Fevers
(3) Contagious Contacts
a. Tuberculosis
b. Salmonellosis
(4) Daycare
a. Cytomegalovirus
b. Tuberculosis
c. Hepatitis
E.
d. Salmonellosis
History: Dietary
(1) Recent potential infectious sources
a. Unpasteurized dairy products
b. Raw Meat
c. Raw Fish
d. Wild rabbit
(2) Pica suggests possible underlying infections
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a. Visceral Larva Migrans
F.
IV.
V.
b. Toxoplasmosis
c. Brucella
d. Salmonellosis
History: Animal Exposure
(1) Dogs or Rodents or their urine (Leptospires)
(2) Pet turtles (Salmonella)
(3) Rats (Rat bite fever)
(4) Cats (Toxoplasmosis)
(5) Parrots or psittacine birds (psittacosis)
(6) Pigeons (Coccidioides)
Physical Exam
Labs: First Line
A.
Complete Blood Count (CBC) with manual differential
B.
Erythrocyte Sedimentation Rate (ESR)
C.
Chemistry panel
D.
Liver Function Tests
E.
Blood Culture
F.
Urinalysis with Urine Culture
G.
Purified Protein Derivative (PPD)
H.
I.
VI.
Chest XRay
Consider Echogram or CT of Abdomen and Pelvis with
contrast
(1) Source found in 19% of patients
Subsequent Evaluation to consider
A.
Infectious cause suspected
(1) Second line tests
a. AFB Sputum Cultures
b. Rapid Plasmin Reagin (RPR)
c. HIV Test
d. ASO Titer
e. Monospot
(2) Third line tests
a. Transesophageal Echocardiogram
1. Evaluate for endocarditis
b. Lumbar Puncture
c. Sinus CT
d. Gallium 67 Scan
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B.
Non-hematologic malignancy suspected
(1) Second line tests
a. Mammogram
b. Chest CT
c. Upper endoscopy
d. Lower endocscopy
e. Gallium 67 Scan
(3) Third line tests
a. Brain MRI
b. Enlarged lymph node biopsy
c. Skin lesion biopsy
C.
D.
VII.
d. Liver biopsy
e. Exploratory laparoscopy
Hematologic malignancy suspected
(1) Peripheral Smear
(2) Serum Protein Electrophoresis
(3) Consider Bone Marrow Biopsy
Autoimmune condition suspected
(1) Rheumatoid Factor
(2) Antinuclear Antibody
(3) Consider temporal artery biopsy
(4) Consider lymph node biopsy
Differential Diagnosis: Occult Bacteremia
A.
Consider hospitalization if fever >2 weeks
B.
Risk factors
(1) Age over 50 years
(2) Diabetes Mellitus
(3) Complete Blood Count: Leukocytosis and Left Shift
(4) Erythrocyte Sedimentation Rate >30
(5) Toxic appearance
(6) Immunocompromised patients
(7) Valvular heart disease
(8) Intravenous Drug Abuse
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