Constantly a part of the natural environment, fungi of the genus Aspergillus usually coexist with humans in harmless symbiosis. In special circumstances, however, some species are an opportunistic pathogen in humans. “Aspergillosis” is actually a spectrum of diverse disorders that include illnesses caused by allergy, colonization, or tissue invasion by Aspergillus spp., including Aspergillus fumigatus, Aspergillus ﬂavus, Aspergillus terreus, Aspergillus niger, Aspergillus versicolor, and others.
ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS
Allergic bronchopulmonary aspergillosis (ABPA) is a
complex hypersensitivity reaction to bronchial colonization with Aspergillus
spp. seen in patients with asthma or cystic ﬁbrosis. The clinical picture
is of the underlying disease with superimposed recurrent episodes of bronchial
obstruction, fever, malaise, expectoration of brownish mucous plugs, peripheral
blood eosinophilia, and at times hemoptysis. Major diagnostic criteria for ABPA
include a history of asthma or cystic ﬁbrosis, immediate skin test reactivity
to Aspergillus antigens, precipitating serum antibodies to A.
fumigatus, serum total IgE concentration greater than 1000 ng/mL,
peripheral blood eosinophilia greater than 500/mL, lung inﬁltrates on chest
radiography or chest computed tomography (CT), central bronchiectasis on chest
CT, and elevated speciﬁc serum IgE and IgG to A. fumigatus.
Oral corticosteroids are the mainstay of treatment of acute ﬂares of ABPA. In patients
requiring frequent or chronic corticosteroids, itraconazole for 3 to 6 months
can reduce the steroid dosage and improve clinical response.
Aspergilli often colonize a preexisting lung cavity
and form an intracavity aspergilloma or fungus ball. The cavity may be the
result of tuberculosis, lung abscess, carcinoma, emphysematous cyst,
histoplasmosis, sarcoidosis, bronchiectasis, or other conditions. Colonized
cavities are more common in the upper lobes, and radiographic ﬁndings are
highly characteristic, showing a rounded mass within the dependent portion of
the cavity, which is capped with a meniscus of air. The mass moves within the
cavity as body position is altered. CT scan and magnetic resonance imaging can
be helpful to better deﬁne the cavity and presence of parenchymal invasion. The
aspergilloma is composed of fungal hyphae, inﬂammatory cells, ﬁbrin, mucus, and
amorphous debris. In most cases, the fungal hyphae do not invade the cavitary
wall but apparently produce enough irritation in some cases to cause mild or
severe hemorrhage. The ﬁnding of a mass within a pulmonary cavity and the
recovery of Aspergillus spp. from multiple sputum cultures are strongly
supportive of the diagnosis of aspergilloma.
Aspergillomas can be asymptomatic; however, hemoptysis
occurs in 75% of patients. If bleeding is severe, frequent, or life
endangering, treatment is indicated. Surgical removal of the fungus ball and
cavity is the preferred mode of treatment. In inoperable patients, oral azole
(itraconazole, voriconazole, or posaconazole) treatment or intracavity
amphotericin B instillation can be of value.
Immunosuppression is as a rule seen in patients with
invasive aspergillosis, including prolonged and severe neutropenia,
glucocorticoid therapy, hematopoietic stem cell and solid organ
transplantation, advanced AIDS, and chronic granulomatous disease. Less
frequently, invasive aspergillosis occurs in patients with solid tumors and in
those who are only mildly immunosuppressed, such as patients with chronic
obstructive pulmonary disease who are taking corticosteroids. From the lungs, which
are most often involved, generalized dissemination may take place to any site.
The course is usually fulminant.
Invasive aspergillosis is characterized by progression
of the infection across tissue planes and vascular invasion with subsequent
infarction and tissue necrosis. The major manifestation is fever that is
unresponsive to broad-spectrum antibiotics; chest pain, cough, and hemoptysis
may also be seen. Chest radiology results can be normal but usually show
nodular lesions, patchy inﬁltrates, or cavitary lesions. On CT imaging, nodules
surrounded by a ground-glass appearance, the so-called “halo sign,” may be
seen; this reﬂects hemorrhage into the tissue surrounding the area of fungal
In seriously immunocompromised patients, Aspergillus
infection may disseminate beyond the respiratory tract and clinically
manifest as sepsis. Infection of virtually any organ can occur, but most
commonly vascular organs such as the kidney, liver, spleen, and central nervous
system are involved.
Diagnosis depends on a combination of clinical
judgment with demonstration of the fungus in tissue specimens obtained from the
presumed site of infection. Serum Aspergillus galactomannan and
-D-glucan assays are useful as diagnostic adjuncts.
Treatment of invasive aspergillosis includes attempts
to reverse the underlying immunosuppression and medical and surgical therapy.
Voriconazole, an azole, has become the initial therapy of choice for patients
with invasive aspergillosis. In patients intolerant of voriconazole, a
lipid-based formulation of amphotericin B can be used. For patients who do not
respond to these ﬁrst-line agents, combinations of an echinocandin (e.g.,
caspofungin) with lipidated amphotericin B or voriconazole can be tried.
Surgery can be used to débride necrotic tissue and to remove infected tissue in