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Aspergillosis is an opportunistic infection caused by inhaling spores of the mold Aspergillus; the spores invade blood vessels, causing hemorrhagic necrosis and infarction. Symptoms may be those of asthma, pneumonia, sinusitis, or rapidly progressing systemic illness. Diagnosis is primarily clinical but may be aided by imaging, histopathology, and specimen staining and culture. Treatment is with voriconazole, amphotericin B (or its lipid formulations), caspofungin, itraconazole, or flucytosine. Fungus balls may require surgical resection. Recurrence is common.
(See also the Infectious Diseases Society of America's Practice Guidelines for Diseases Caused by Aspergillus.)
Aspergillus sp are among the most common environmental molds, frequently present in or on the following:
Pathophysiology
Invasive infections are usually acquired by inhalation of spores or, occasionally, by direct invasion through damaged skin.
Major risk factors include
Aspergillus sp tends to infect open spaces, such as pulmonary cavities caused by previous lung disorders (eg, bronchiectasis, tumor, TB), the sinuses, or ear canals (otomycosis). Such infections tend to be locally invasive and destructive, although systemic spread sometimes occurs, particularly in immunocompromised patients.
A. fumigatus is the most common cause of invasive pulmonary disease; A. flavus most often causes invasive extrapulmonary disease, probably because these patients are more severely immunosuppressed than patients infected with A. fumigatus.
Focal infections, typically in the lung, sometimes form a fungus ball (aspergilloma), a characteristic growth of tangled masses of hyphae, with fibrin exudate and few inflammatory cells, typically encapsulated by fibrous tissue. Occasionally, there is some local invasion of tissue at the periphery of the cavity, but usually the fungus just resides within the cavity with no appreciable local invasion.
A chronic form of invasive aspergillosis occasionally occurs, particularly in patients with chronic granulomatous disease, which is characterized by a hereditary phagocytic cell defect. Aspergillus sp can also cause endophthalmitis after trauma or surgery to the eye (or by hematogenous seeding) and infections of intravascular and intracardiac prostheses.
Primary superficial aspergillosis is uncommon but may occur in burns; beneath occlusive dressings; after corneal trauma (keratitis); or in the sinuses, mouth, nose, or ear canal.
Allergic bronchopulmonary aspergillosis is a hypersensitivity reaction to A. fumigatus that results in lung inflammation unrelated to fungal invasion of tissues (see Asthma and Related Disorders: Allergic Bronchopulmonary Aspergillosis (ABPA)).
Symptoms and Signs
Chronic pulmonary aspergillosis causes cough, often with hemoptysis and shortness of breath. If untreated, invasive pulmonary aspergillosis usually causes rapidly progressive, ultimately fatal respiratory failure.
Extrapulmonary invasive aspergillosis begins with skin lesions, sinusitis, or pneumonia and may involve the liver, kidneys, brain, and other tissues; it is often rapidly fatal.
Aspergillosis in the sinuses can form an aspergilloma or cause allergic fungal sinusitis or a chronic, slowly invasive granulomatous inflammation with fever, rhinitis, and headache. Patients may have necrosing cutaneous lesions overlying the nose or sinuses, palatal or gingival ulcerations, signs of cavernous sinus thrombosis, or pulmonary or disseminated lesions.
Diagnosis
Because Aspergillus sp are common in the environment, positive sputum cultures may be due to environmental contamination or noninvasive colonization in patients with chronic lung disease; positive cultures are significant mainly when obtained from patients with increased susceptibility due to immunosuppression or when there is high suspicion due to typical imaging findings. Conversely, sputum cultures from patients with aspergillomas or invasive pulmonary aspergillosis are often negative because cavities are often walled off from airways and because invasive disease progresses mainly by vascular invasion and tissue infarction.
Chest x-rays are taken, and CT of sinuses is done if sinus infection is suspected. A movable fungus ball within a cavitary lesion is characteristic on both, although most lesions are focal and solid. Sometimes imaging detects a halo sign (a thin air shadow surrounding a nodule), representing cavitation within a necrotic lesion. Diffuse, generalized pulmonary infiltrates are seen in some patients.
Culture and histopathology of a tissue sample are usually necessary for confirmation; the sample is typically taken from the lungs via bronchoscopy and from the sinuses via anterior rhinoscopy. Because cultures take time and histopathology results may be false-negative, most decisions to treat are based on strong presumptive clinical evidence. Large vegetations often release sizable emboli that may occlude blood vessels and provide specimens for diagnosis.
Various serologic assays exist but are of limited value for rapid diagnosis of acute, life-threatening invasive aspergillosis. Detection of antigens such as galactomannans can be specific but is not sufficiently sensitive to identify most cases in their early stages. Blood cultures are almost always negative, even in rare cases of endocarditis.
Treatment
Invasive infections usually require aggressive treatment with IV amphotericin B or voriconazole (generally considered the first-choice drug). Oral itraconazole (but not fluconazole) can be effective in some cases. Caspofungin or other echinocandins may be used as salvage therapy. Combination therapy with azoles and echinocandins or with amphotericin B and echinocandins has been effective in some patients.
Usually, complete cure requires reversal of immunosuppression (eg, resolution of neutropenia, discontinuation of corticosteroids). Recrudescence is common if neutropenia recurs.
Aspergillomas neither require nor respond to systemic antifungal therapy but may require resection because of local effects, especially hemoptysis.
Last full review/revision April 2009 by Alan M. Sugar, MD
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