Aspergillosis

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: leukemia, bone marrow or organ transplant, late HIV infection

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

• Serologic detection in serum or other body fluids

  • Useful for early diagnosis and treatment

  • However, multiple determinations should be done and usefulness is decreased in patients receiving anti-mold prophylaxis (ie, voriconazole or posaconazole)

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

  • Patchy infiltration leading to a severe necrotizing pneumonia

  • Tissue infarction (development of pleuritic chest pain and elevation of serum lactate dehydrogenase [LD])

  • Hematogenous dissemination to the CNS, skin, and other organs

  • Blood cultures have very low yield

  • Detection of galactomannan by enzyme-linked immunosorbent assay (ELISA) or Aspergillus DNA by polymerase chain reaction (PCR); multiple determinations should be done

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

  • Chest CT scan may show indicative characteristics (eg, "halo sign")

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, although voriconazole is increasingly being used

• Allergic aspergillus sinusitis

  • Topical corticosteroids cornerstone of therapy

  • Itraconazole is best studied agent

• Chronic aspergillosis

  • Surgical resection remains most effective therapy for symptomatic aspergilloma

  • Other forms of chronic aspergillosis are generally treated with at least 4–6 months of oral azole therapy

    • Itraconazole, 200 mg twice daily

    • Voriconazole, 200 mg twice daily

    • Posaconazole, 300 mg daily

• Invasive aspergillosis

  • Reversal of any correctable immunosuppression

  • Rapid institution of voriconazole (6 mg/kg intravenously twice on day 1 and then 4 mg/kg every 12 hours thereafter) is considered optimal therapy

  • Combination therapy ...