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Fever of Unknown Origin 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 Kaposi’s 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 patient’s still have favorable outcomes. Diagnosis Comprehensive History Physical Exam Confirm fever and document pattern 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. Diagnosis of Fever of Unknown Origin 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 CT of abdomen or pelvis with contrast agent Malignancy, inflammation Transthoracic or transesophageal echocardiography Malignancy, autoimmune conditions PET scan Acute infection and inflammation of bones and soft tissue MRI of brain Occult septicemia Technetium Tc 99m Infection, malignancy Indium-labeled leukocytes Abscess, malignancy Gallium 67 scan Tuberculosis, malignancy, Pneumocystis carinii pneumonia Bacterial endocarditis Venous Doppler study Venous thrombosis 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.