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1 2010 21 204-209 6609 Basalt Drive, Plano, Texas, USA 75024 (Retired Blog address ) 1961 Petersdorf Beeson Paul Beeson Yale Robert Petersdorf 1 Fever of Unknown Origin (FUO) FUO FUO 1. 101 2. 3. work-up FUO 30-40% 20-30% 10-20% collagen-vascular diseases 5-15% human immunodeficiency virus (HIV) FUO 1961 Petersdorf Beeson ( human immunodeficiency virus, HIV) Fever of unknown origin.

2 FUO Endocarditis Tuberculosis Arteritis FUO FUO 2-5 classic FUO ( ) nosocomial FUO immune-deficiency FUO HIV-associated FUO (Classic) FUO FUO ("intelligent and invasive" investigation) Classic FUO ( ) abscesses, endocarditis, tuberculosis, complicated urinary tract infec-tions ( ) neoplasms lymphomas, leukaemias ( ) (connective tissue dise-ases) (temporal arteritis), polymyalgia rheumatica, Still 's disease, systemic lupus ery-thematosus, rheumatoid arthritis ( ) alcoholic hepatitis, granulomatous conditions ( computerized tomography = CT FUO ) ( ) FUO catheters ( Clostridium difficile colitis drug fever) immobilization ( ) deep vein thrombosis (DVT) acalculous cholecystitis adrenal insufficiency FUO neutrophils 6 HIV FUO 7 HIV FUO (fictitious fever) (Antibiotics Epilepsy medications Immune globulin Antipsychotics Thorazine, Haldol = haloperidol Anti-histamines)

3 FUO FUO FUO History taking (past medical history)( ) ( )( white blood cell count=WBC )( ) ( WBC )( ) ( )( ) ( ) ( )( ) ( ) ( ) (family history)205 ( ) ( ) ( )( ) (personal history)( ) ( ) ( ) ( ) ( ) (travel history)( ) ( ) contacts)( ) ( ) [rabies virus, SARS (severe acute respiratory syndrome) corona virus, Nipah virus ]( ) ( ) (factitious fever ) ( ) (intermittent) (continuous) recurrent brucellosis borreliosis Hodgkin's disease 8 ( ) eschar 9 Complete blood count (CBC) blood smear ( ) hemoglobin (Hgb) hematocrit (Hct) mean corpuscular volume (MCV) mean corpuscular hemoglobin (MCH)

4 MCH MCV normochromic, normocytic anemia hypochromic, mic-rocytic anemia ( ) WBC left shift WBC left shift ( ) WBC ( ) leukocytosis ( ) WBC ( ) leukocyte blast cell pre-leukemic phase aleukemia ( ) atypical lymphocytes herpes viruses HIV herpes ( ) disseminated intravascular co-agulation ( ) malaria filariasis 206 Urinalysis atypical mycobacterium(Mycobac-terium smegmatis ) Serum chemistry ( ) lactic dehydrogenase (LDH) ( ) C-reactive protein (CRP) ( ) pleural effusion, ascites, CSF= cerebrospinal fluid ( ) 85-95% Culture-negative endocarditis ( ) CSF ( ) titer intern routine IgM ( ) Brucellosis, CMV (cytomegalovirus)

5 Infection, infectious mononucleosis, HIV infection, amebiasis, toxoplasmosis, and chlamydial diseases Other tests( ) Systemic lupus erythematosus, rheum-atoid arthritis, thyroiditis, hyperthyroidism, giant cell arteritis (GCA), polymyalgia rheumatica (PMR) erythrocyte sedimentation rate (ESR) antinuclear antibody(ANA) GCA PMR ESR 60 ( ) Kikuchi(-Fujimoto) disease biopsy (Imaging Studies)9 CXR (chest X-ray), PA (posterior-antierior) and lateral Abdominal ultrasono-graphy CT scanning FUO work-up CT MRI = magnetic resonance imaging IVP Intravenous pyelography CT retroperitoneal space CT (MRI) (osteomyelitis) (vasculitis) retrograde cholangiography Crohn disease, Whipple disease, Ventilation and perfusion radionucleotide scan pulmonary angiogram pul-monary emboli Gallium-67 scan Indium-111 scan Technetium bone scan Positron emission tomography (PET) scanning Transesophageal Echocardiogra-phy(TEE) vegetations 207 9 ( ) culture-negative end-ocarditis ( ) ( ) temporal arteritis GCA ( )

6 Culture-negative endocarditis prosthetic valve penicillin vancomycin gentamicin rifampicin Q fever doxycycline Therapeutic trial ( ) INH 300 mg + EMB 800 mg + RIF 600 mg ( 50 450 mg) + PZA 1,500 mg Rifater + EMB ESR ( ) temporal arteritis hydorcortisone 100 mg, q6h prednisolone 60-100 mg/day temporal artery biopsy FUO RG, Beeson PB. Fever of unexplained origin: report on 100 cases. Medicine 1961; 40: 1-30. 2. Roth AR, Basello GM. Approach to the adult patient with fever of unknown origin.

7 Am Fam Physician 2003; 68: 2223-8. 3. Durack DT, Street AC. Fever of unknown origin - re-examined and redefined. Curr Clin Top Infect Dis 1991; 11: 35-51. 4. Konecny P, Davidson RN. Pyrexia of unknown origin in the 1990s: time to redefine. Br J Hosp Med 1996; 56: 21-4. 5. Cunha BA. Fever of unknown origin. Infect Dis Clin North Am 1996; 10: 111-27. 6. Hughes WT, Armstrong D, Bodey GP, et al. Guidelines for the use of antimicrobial agents in neutropenic patients with unexplained fever. J Infect Dis 1990; 161: 381-96. 7. Armstrong WS, Katz JT, Kazanjian PH. Human immu-nodeficiency virus - associated fever of unknown origin: a study of 70 patients in the United States and review. Clin Infect Dis 1999; 28: 341-5. 8. Mackowiak PA. Commentary. Fever patterns. Infect Dis Clin Practice 1997; 6: 308-9.

8 9. Chan-Tack KM, Bartlett J. Fever of unknown origin. eMedicine, Dec. 7, 2009. 208 Fever of Unknown OriginClement C. S. Hsu(Retired Blog address )Clinical definition of the "fever of unknown origin" was delineated nearly 50 years ago by Petersdorf and Beeson. Since then, there have been numerous breakthroughs in the DNA and imaging technology. These advances have simplified and shortened the durations required to clarify diseases that were previously difficult to diagnose. However, the appearance of human immunodeficiency virus (HIV) infection and invasive therapeutic maneuvers have added new dimensions to the causes of the FUO. Despite all the advances in technology, a thorough, detailed history taking can never be ignored. The work-up is better be carried out under the supervision of qualified infectious disease specialist.

9 Therapeutic trials are limited only to a few situations. When no definitive cause could be found, patients should be put under close observations. Depending on the patients' condition and possible new signs and symptoms, all or specific exams should be repeated. Those who have prolonged fever without significant weight loss are unlikely to have malignant diseases. ( J Intern Med Taiwan 2010; 21: 204-209 )209