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- A spectrum of diseases caused by species of the ubiquitous mold, Aspergillus
- Saprophytic: chronic pulmonary aspergillosis (CPA), aspergilloma, chronic cavitary, chronic fibrosing, chronic necrotizing pulmonary aspergillosis (CNPA)
- Allergic: allergic bronchopulmonary aspergillosis (ABPA), Aspergillus hypersensitivity (AH)
- Invasive: invasive aspergillosis (IA)
- Infection usually involves the lungs and sinuses; GI, ophthalmologic, CNS, and skin less common
- Aspergillus spp. are ubiquitous, distributed worldwide, found in decomposing plant matter.
- Affects patients of all ages, no gender predominance
- CPA typically involves older patients with structural pulmonary abnormalities.
- Chronic obstructive pulmonary disease (COPD) and tuberculosis increase risk of CPA.
- Aspergillosis is the most frequent invasive fungal infection in hematopoietic stem cell transplantation (HSCT) patients.
- ABPA incidence is 1–4% in patients with asthma and 7–9% in patients with cystic fibrosis (CF).
- IA incidence in allogeneic and autologous HSCT is 2–15% and 0.5–4%, respectively.
- IA incidence may be as high as 6% in ICU patients, many of whom lack classic risk factors.
- Cutaneous involvement in 1% of IA; most patients have underlying hematologic malignancies.
- ABPA prevalence is 13% in asthma.
- CPA prevalence is <1 in 100,000 in the United States; higher in Asia and Africa
Etiology and Pathophysiology
- Inhalation is the most common route of entry for Aspergillus spores.
- ABPA results from an exaggerated immune response. Milder responses can result in AH.
- Aspergillomas form within existing lung cavities when spores germinate and create mass of hyphae.
- Alveolar macrophages are the first line of phagocytic host defense against Aspergillus sp. Neutrophils are the predominant immune defense against hyphae (explaining the high risk of IA in neutropenic patients).
- Aspergillus fumigatus is responsible for most clinically significant disease (>67%); Aspergillus flavus, Aspergillus niger, and Aspergillus terreus also pathogenic
- Cutaneous manifestations may result from direct inoculation or systemic spread of invasive disease.
- Patients with atopy, asthma, and CF are at greatest risk for developing AH and ABPA.
- All patients with asthma should be routinely screened for ABPA using A. fumigatusspecific IgE levels.
- CPA occurs primarily in patients with structural lung disease (COPD, cavitary tuberculosis, bronchiectasis, sarcoidosis, or bronchocentric carcinoma), particularly patients treated with high-dose corticosteroids.
- IA is an opportunistic infection found in severely immunocompromised hosts.
- Neutropenia predisposes patients to IA, particularly if severe (<100 cells/μL), prolonged (>10 days), or associated with aplastic anemia, current chemotherapy, leukemia, solid organ transplant, or HSCT. Highest risk is in HSCT, lung transplantation, and congenital or acquired immunodeficiency syndromes.
- Genetic deficiency of receptor pentraxin 3 (PTX3, affects neutrophil antifungal activity) may increase risk for IA after HSCT.
- Patients on long-term steroids or anti-TNF agents are at risk of IPA.
- Treat preexisting lung disease.
- Prophylaxis with posaconazole reduces risk of IA in highest risk patients, including allogeneic HSCT recipients with graft-versus-host disease (GVHD) and neutropenic patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) who are receiving chemotherapy.