The osler medical handbook -john hopkin

infectious diseases

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Piccini & Nilsson: The Osler Medical Handbook, 2nd ed., Copyright © 2006 Johns Hopkins University

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Section VIII - Infectious Diseases

Section Editors:

Christopher Hoffmann, MD, MPH Nicola Zetola, MD

Chapter 53 - Fever of Unknown Origin

Scott Kim, MD Rachel Damico, MD, PhD Paul Auwaerter, MD

FAST FACTS

▪ The contemporary understanding of fever of unknown origin (FUO) is derived from Petersdorf and Beeson's 1961 characterization of FUO. A stringent definition of FUO is composed of the following criteria[1]: temperature higher than 38.3° C measured on several occasions, 3-week duration (to exclude self-limiting fevers), negative blood cultures, no apparent explanation, and three outpatient visits or three hospital days.

▪ Infections, malignancies, and noninfectious inflammatory diseases account for the majority of cases of FUO.

▪ In patients older than 65 years, temporal arteritis should be considered early in any evaluation.

▪ Patients with FUO who remain undiagnosed after exhaustive study usually have a favorable prognosis. In one study, in a cohort of 61 patients with FUO discharged without diagnosis, the 5-year mortality rate was only 3.2%.[2]

I. EPIDEMIOLOGY

1. The majority of identifiable causes of FUO can be grouped into four specific disease categories: infections, neoplasms, noninfectious inflammatory diseases, and miscellaneous causes.[3]

2. The prevalence of different causes has changed over the past five decades including an increase in the relative proportion of patients who remain undiagnosed because of improvements in laboratory and radiologic diagnostic techniques ( Fig. 53-1 ).[4]

3. FUO often is subdivided into four subcategories: classic FUO, FUO associated with the human immunodeficiency virus (HIV; see Chapter 52 ), neutropenic FUO, and nosocomial FUO ( Table 53-1 ).[5]

4. Tuberculosis, endocarditis, and intraabdominal abscesses are the most commonly reported infectious causes of FUO, although more extensive use of computed tomography (CT) scanning is leading to earlier diagnosis of intraabdominal abscesses. The most common malignancies implicated in FUO are Hodgkin's lymphoma and non-Hodgkin's lymphoma. Temporal arteritis accounts for 15% to 16% of FUO diagnoses in older adults.[5]

FIG. 53-1 Trends in the causes of fever of unknown origin. (Modified from Mourad O et al: Arch Intern Med 163:545-551, 2003.)

TABLE 53-1 -- CLASSIFICATION OF FEVER OF UNKNOWN ORIGIN

Category Patient Population Minimal Duration of Investigation Typical Causes

HIV associated Confirmed HIV positive 3 d of inpatient investigation or 4 wk of outpatient studies Mycobacterial infection (Mycobacterium avium- intracellulare and Mycobacterium tuberculosis), non-Hodgkin's disease, drug fever

Neutropenic Absolute neutrophil count ≤ 500/mm3 or in decline 3 d Bacterial infections, aspergillosis, candidemia

Nosocomial Hospitalized in an acute care setting (not admitted with infection) 3 d Pulmonary embolus, sinusitis, Clostridium difficile colitis, drug fever

Classic All others with fever ≥ 3 wk 3 d of inpatient investigation or 3 outpatient visits Infection, neoplasm, noninfectious inflammatory diseases