ABSTRACT
Invasive fungal infections are principally encountered in patients who are seriously immunosuppressed over a long period of time (1). These opportunistic infections occur particularly in those with an impaired cellular immunity and/or a severe granulocytopenia (2,3). This association has crucial repercussions for both establishing the diagnosis and instituting an appropriate therapy. Granulocytes are supposed to protect an individual against opportunistic pathogens and this reaction accounts under normal circumstances for most signs and symptoms that may accompany a serious local and, subsequently, invasive fungal infection. As a consequence of the low number of granulocytes, the inflammatory reaction is muted and the absence of infiltrating white cells around the germinating fungi prohibits an early radiological diagnosis, which has in turn consequences for the management of these diseases (4). More than one-third of patients in whom an invasive fungal infection was found at autopsy never received any antifungal therapy, which indicates that the symptoms of an active and, obviously, lethal fungal infection are neither alarming nor very typical (1). Even in non-neutropenic patients, the diagnosis of an invasive fungal infection may be problematic because the clinical presentation is nonspecific and variable, related to the organs afflicted. Moreover, sometimes patients do not appear to be seriously endangered because the accompanying symptoms are ameliorated by concomitantly administered anti-inflammatory drugs. Because of the suppression of the fever by concurrent corticosteroids, even patients suffering from chronic disseminated mycoses may feel relatively well until the infection progresses and organ failure becomes evident. The fact that a large proportion of these opportunistic infections affect critically ill patients at the extremes of age is a further explanation for the paucity of symptoms. In addition, it has to be emphasized that the clinical picture
can be disturbed by coexisting other infections too; they appear to play a role in a significant proportion of patients (5). The perturbed inflammatory reaction as a result of a low number of granulocytes, often in combination with immune modulating drugs, is responsible for a very wide spectrum of diseases, especially because chemotherapy-induced granulocytopenia is not a constant factor. It is a rather dynamic process with a time-dependent increase or decrease in the number of immune reactive cells. Upon return of the granulocytes, the clinical signs and symptoms will become readily detectable but in many cases, the infection would have reached an advanced stage by then (6). As is apparent from Table 1, there are very few clinical signs that can be regarded as characteristic for a particular invasive fungal infection. Fever, being present in 99% of the episodes, appears to be the only consistent signal of a possible, acute infection. This applies not merely to common organisms such as Candida and Aspergillus species but also to endemic mycoses, as well as to the emerging, more rare fungi like zygomycetes (mucormycosis), Fusarium, Scedosporium/Pseudallescheria, Saccharomyces, and Rhodotorula species. All of these organisms have occasionally been associated with life-threatening systemic symptoms and shock, but quite commonly unexplained fever is the first manifestation (7-14).
