Fever of Unknown Origin

Morning ReportAugust 9, 2005Hili Morillas, MD

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 abscessesPelvic abscessesDental abscessesEndocarditisOsteomyelitisSinusitisCytomegalovirusEpstein-Barr virusHuman immunodeficiency virusLyme diseaseProstatitisSinusitis

Infections As duration of fever increases,

infectious etiology decreases Malignancy and factitious fevers are

more common in patients with prolonged FUO.

Malignancies Chronic leukemia

LymphomaMetastatic cancersRenal cell carcinomaColon carcinomaHepatomaMyelodysplastic syndromesPancreatic carcinomaSarcomas

Autoimmune Adult Still's disease

Polymyalgia rheumaticaTemporal arteritisRheumatoid arthritisRheumatoid feverInflammatory bowel diseaseReiter's syndromeSystemic lupus erythematosusVasculitides

Miscellaneous Drug-induced fever

Complications from cirrhosisFactitious feverHepatitis (alcoholic, granulomatous, or lupoid)Deep venous thrombosisSarcoidosis

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 Tuberculosis, malignancy, Pneumocystis carinii pneumonia

CT of abdomen or pelvis with contrast agent Abscess, malignancy

Gallium 67 scan Infection, malignancy

Indium-labeled leukocytes Occult septicemia

Technetium Tc 99m Acute infection and inflammation of bones and soft tissue

MRI of brain Malignancy, autoimmune conditions

PET scan Malignancy, inflammation

Transthoracic or transesophageal echocardiography 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.