Journal of the Louisiana State Medical Society
DIAGNOSIS: Disseminated, invasive aspergillosis
Aspergillus is a rare entity, accounting for only one-quarter of all fungal causes of infective endocarditis. 8 In 2010, Kalokhe et al. reviewed approximately 50 cases of Aspergillus endocarditis and described the following notable features: vegetations that were large in size, most often situated on the mitral valve (49%), but multi-valvular in 21% of cases. Valvular destruction was common, and systemic vascular emboli were frequently demonstrated. Patients were more oftenmale and possessed an underlying preexisting cardiac abnormality such as coronary artery disease or prosthetic valves. 8 Based on these features we conclude that, in the case presented here, a primary respiratory aspergillosis with pul- monary venous spread initially to the left heart was a more likely nidus for the invasion and subsequent dissemination than a primary multi-valve endocardial infection. The diagnosis of invasive aspergillosis is based mainly upon isolating the organism either by microbiologic culture or by histopathologic demonstration of the organism in tis- sue, as seen in the current case. Initial clinical suspicion for invasive aspergillosis, however, remains a challenge in so much that symptoms may be entirely nonspecific such as fever, chest pain, cough, malaise, and dyspnea, or without any respiratory symptomatology at all, as is reported to be the case in up to 40%. 9 Though tissue diagnosis does require invasive biopsy, major advantages of histology include diagnostic speed, low-cost, and its ability to demonstrate adjacent tissue reaction, such as necrosis, to the fungal ele- ments. Routine histology favors the use of the hematoxylin and eosin (H&E) stain. Though H&E does have the capacity to stain Aspergillus , it is limited in its identification of other fungi and is frequently supplemented by additional stains such as Gomori’s methenamine siliver (GMS) and periodic acid-Schiff (PAS) so that fungal morphology can be better highlighted. The images submitted for the current case (Figure 1 A, B, and C) illustrate the characteristic features of invasive Aspergillus as seen on H&E, GMS, and PAS, as well as the typical tissue response associated with the fungal infection. Despite perceived advances in antifungal therapies, invasive and, moreover, disseminated aspergillosis remain devastating opportunistic infections. On the basis of autopsy literature, the number of Aspergillus -related deaths increased by a factor of four in the United States during the 1980s and 1990s, presumably a reflection not only of the increasing number of immunocompromised patients but also of the high associated mortality. 10 In a 1996 review of more than 1,000 cases, Denning found a case-fatality rate (CFR) of 99%, 86%, and 66% for cerebral, pulmonary, and sinus invasive aspergillosis, respectively. 11 More recently, in a case series and systematic literature review, the CFR for central nervous system (CNS) Aspergillus , as seen in the current case, was confirmed to be uniformly fatal and the highest of all forms of invasive aspergillosis. 12 Despite the growing number of cases of invasive aspergillosis in presumably immunocom- petent individuals, the prognosis appears to be consistently grim with comparable fatality rates. 6 The unfortunate case presented here of disseminated,
DISCUSSION Aspergillosis is a constellation of clinical diseases all caused by the fungal pathogen of Aspergillus . Aspergillus is a highly aerobic fungus with the capacity to infect almost every major organ system. With more than 60 pathogenic species, the two known to most frequently cause human infection are A. fumigatus and A. flavus . 1 Localized, single organ Aspergillus is most frequently seen in the lung. When the pattern is that of a stable, singular, nonprogressive fungal ball within the lung parenchyma, it is known as an aspergilloma, and the patient complains of few symptoms. More complex cystic nodules can be seen, however, with progressive cavitation andmore advanced symptoms, typi- cally called chronic cavitary, complex or chronic necrotizing aspergillosis. 2 Tissue invasion by Aspergillus , a.k.a. invasive aspergil- losis, has long been known to pose a significant threat to the immunocompromised individual, with the first reported case dating back to 1953. 3 Since its initial report, the litera- ture has cited up to a 150% relative increase in cases 4 due largely to the expanding profile of patients considered at risk for tissue invasion by Aspergillus, which includes those undergoing chemotherapy, transplant patients - both bone marrow and solid organ - those on immunosuppressive regimens including high-dose, prolonged corticosteroids; patients with chronic granulomatous disease; and those affected by advanced human immunodeficiency virus (HIV) and AIDS. 2,5 Widespread or systemic dissemination of Aspergillus , also ascribed to the immunocompromised in- dividual, is diagnosedwhen Aspergillus infection is detected in >1 noncontiguous site, thus reflecting blood-borne spread. This is in contrast to multi-site Aspergillus that occurs within one contiguous organ system, such as might be the case in infection involving both the lung and the sinonasal tract. 6 More recently, there has been a growing body of literature reporting invasive aspergillosis in immuno- competent individuals without the classical risk factors. These non-traditional patients appear, however, to have several comorbidities in common and can be categorized into those who have conditions such as chronic obstructive pulmonary disease, diabetes, liver failure, alcoholism, and malnutrition. 2 In one study of approximately 40 patients with documented invasive Aspergillus in the intensive care unit (ICU), more than one-half of the patients (54%) had none of the widely accepted determinants of increased risk for invasive aspergillosis. 7 In cases of disseminated aspergillosis, the primary site of origin is most often reported to be that of the respiratory tract. As a ubiquitous soil borne fungus that survives and grows on organic debris, the Aspergillus conidia have a diameter small enough to reach the alveoli of the lung (2-3 u m ). As such, aspergillosis has become the most prevalent airborne fungal pathogen. By contrast, endocarditis due to
94 J La State Med Soc VOL 166 March/April 2014
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