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 ...