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 invasion.
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 selected patients.