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For further information, see CMDT Part 36-07: Aspergillosis

Key Features

Essentials of Diagnosis

  • Most common cause of noncandidal invasive fungal infection in transplant recipients and in patients with hematologic malignancies

  • Predisposing factors for invasive disease: leukemia, bone marrow or organ transplantation, corticosteroid use, advanced AIDS

  • Lungs, sinuses, and CNS are most common disease sites

  • Detection of galactomannan in serum or other body fluids is useful for early diagnosis in at-risk patients

General Considerations

  • Aspergillus fumigatus is the usual cause of aspergillosis, although many species of Aspergillus can cause disease

  • Clinical illness results from abnormal immune response or tissue invasion

  • Allergic bronchopulmonary aspergillosis (ABPA) occurs in persons with asthma or cystic fibrosis

  • Invasive aspergillosis

    • Usually occurs in profound immunodeficiency, particularly in patients

      • Who have undergone hematopoietic stem cell transplantation

      • With prolonged severe neutropenia

    • Can occur among critically ill immunocompetent patients

Clinical Findings

  • Allergic forms of aspergillosis

    • ABPA causes worsening bronchospasm in patients with asthma or cystic fibrosis

    • Allergic aspergillus sinusitis produces a chronic sinus inflammation characterized by eosinophilic mucous and noninvasive hyphal elements

  • Chronic aspergillosis

    • Cough

    • Shortness of breath

    • Weight loss

    • Malaise

  • Invasive aspergillosis

    • Pulmonary disease most common

    • Invasive sinus disease

Diagnosis

  • ABPA

    • Eosinophilia

    • High levels of total IgE, and IgE and IgG specific for Aspergillus in the blood

  • Chronic aspergillosis

    • Disease manifestations range from aspergillomas that develop in a lung cavity to chronic fibrosing pulmonary aspergillosis in which the majority of lung tissue is replaced with fibrosis

  • Invasive aspergillosis

    • Definitive diagnosis requires demonstration of Aspergillus in tissue or culture from a sterile site

    • Indirect diagnostic assays include detection of galactomannan in bronchoalveolar lavage fluid or serum, or serum assays for (1, 3)-beta-D-glucan (though the latter is not specific for Aspergillus); the diagnostic utility of Aspergillus DNA by PCR is debated

    • To improve the reliability of galactomannan testing, multiple determinations should be done, though sensitivity is decreased in patients receiving anti-mold prophylaxis (ie, voriconazole or posaconazole)

    • Galactomannan levels and Aspergillus DNA PCR can be tested in serum or in bronchoalveolar lavage fluid, which may be more sensitive than serum

    • Isolation of Aspergillus from pulmonary secretions does not necessarily imply invasive disease, although its positive predictive value increases with more advanced immunosuppression

    • CT scanning of the chest may aid in early detection and help direct additional diagnostic procedures

    • Common radiologic findings include

      • Nodules

      • Wedge-shaped infarcts

      • Characteristic "halo sign," a zone of diminution of ground glass around a consolidation

Treatment

  • ABPA

    • For acute exacerbations, prednisone, 0.5 mg/kg/day orally tapered slowly over several months

    • Itraconazole, 200 mg orally once daily for 16 weeks, appears to improve pulmonary function and decrease corticosteroid requirements

    • Voriconazole is an alternative agent

  • Allergic aspergillus sinusitis

    • Topical corticosteroids cornerstone of therapy

    • Itraconazole is best studied agent

  • Chronic aspergillosis

    • Surgical resection is most effective therapy for symptomatic aspergilloma

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