Fever of unknown origin or fever of too many origins?

n engl j med 368;3 nejm.org january 17, 2013o 197 as they define it — a tempera­ ture rising above 38.3°C (101°F) on several occasions over a peri­ od of more than 3 weeks, for which no diagnosis has been reached despite 1 week of inpa­ tient investigation — is con­ sidered classic FUO. In the past 60 years, clinician­scientists have tracked the changing causes of these problematic fevers, as dis­ ease patterns and definitions have changed and as improved serologic and imaging technolo­ gies have begun revealing diag­ noses more quickly. The standard definition of FUO no longer in­ cludes the requirement for a week of inpatient evaluation. And in the early 1990s, Durack and Street proposed dividing FUOs into four groups: classic, nosocomial, neu­ tropenic, and HIV­associated.2 According to Petersdorf and Beeson’s original report, FUOs were caused by infection (in 36% of patients), malignancy (19%), collagen vascular diseases (19%), and miscellaneous other causes (19%), such as drug fever.1 No cause was determined in 7% of patients. It is paradoxical that despite the introduction of com­ puted tomography (CT), magnetic resonance imaging, improved cul­ ture techniques, numerous new serologic assays, and polymerase­ chain­reaction studies, in recent years more FUOs have actually eluded diagnosis. In 2003, Vander­ schueren and colleagues reported that in nearly a third of 290 im­ munocompetent patients in Bel­ gium, no diagnosis was made,3 and in 2007, Bleeker­Rovers et al. reported that among 73 immu­ nocompetent patients from five hospitals in the Netherlands, no cause of FUO was identified in 51% of cases.4 As an infectious­disease physi­ cian who has practiced at academ­ ic, tertiary care facilities in the metropolitan New York area for nearly three decades, I’ve been struck by the fact that traditionally caused FUOs are now rarer than the FUOs that I’m increasingly asked to evaluate. The new FUOs are often found in patients in the intensive care unit (ICU) who have traumatic brain injury, other neu­ rologic events, or dementia; are mechanically ventilated; have some combination of urethral, central, and peripheral catheters placed; have recently undergone surgery; and are already receiving multiple broad­spectrum antibiotics. How­ ever, they continue to spike multi­ ple fevers daily for weeks and sometimes months on end, usually without other signs or symptoms of sepsis. Physical examination often re­ veals edema (if not anasarca), early decubital ulcers in the sacral region at minimum, cuta­ neous eruptions that do not ap­ pear to be drug­related, mild ab­ dominal distention, wounds that Fever of Unknown Origin or Fever of Too Many Origins?