Aspergillosis

KEY FEATURES

Essentials of Diagnosis

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

• Risk factors for invasive disease

  • Leukemia

  • Hematopoietic stem cell or solid-organ transplantation

  • Corticosteroid use

  • AIDS

  • COVID-19 coinfection

• Pulmonary, sinuses, and central nervous system (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; lungs, sinuses, and brain are the organs most often involved

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

• Chronic pulmonary aspergillosis

  • Usually occurs when there is preexisting lung damage without significant immunocompromise

  • Manifestations range from aspergillomas in a lung cavity to chronic fibrosing pulmonary aspergillosis where the majority of lung tissue is replaced with 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

  • Tracheobronchitis and pulmonary aspergillosis have been observed in association with severe COVID-19 infection (termed COVID-19–associated pulmonary aspergillosis)

CLINICAL FINDINGS

• Allergic forms of aspergillosis

  • Occurs in patients with preexisting asthma or cystic fibrosis

  • Worsening bronchospasm

  • Fleeting pulmonary infiltrates

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

• Chronic aspergillosis

  • Long-standing symptoms (> 3 months)

  • Cough

  • Shortness of breath

  • Weight loss

  • Malaise

• Invasive aspergillosis

  • Pulmonary disease most common; patchy infiltration leading to a severe necrotizing pneumonia

  • Invasive sinus disease

  • Has been observed in severe COVID-19 infection (called COVID-19–associated pulmonary aspergillosis, or CAPA)

DIAGNOSIS

Laboratory Tests

• ABPA

  • Eosinophilia

  • High levels of IgE and IgG Aspergillus precipitins in the blood

• Invasive aspergillosis

  • Elevation of serum lactate dehydrogenase [LD]) from tissue infarction

  • Blood cultures have very low yield

  • Aspergillus DNA in serum or bronchoalveolar lavage may be useful, particularly when used with other biomarkers

  • Galactomannan (component of the Aspergillus cell wall)

    • May be recovered in serum or bronchoalveolar lavage

    • Serial determinations of serum galactomannan improve the test reliability

  • Serum assays for (1,3)-beta-D-glucan (a fungal cell wall component that is not specific for Aspergillus)

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

Imaging

• • Invasive aspergillosis: chest CT scan may show

    • Nodules or wedge-shaped infarcts

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

Diagnostic Procedures

• Isolation of Aspergillus from pulmonary secretions

  • Not definitive for invasive disease

  • Positive predictive value increases with more advanced immunosuppression