Aspergillosis¶
Chapter 223 | Part 5: Infectious Diseases
KEY CLINICAL POINTS¶
- Aspergillosis encompasses invasive, chronic, and allergic forms caused by ~50 Aspergillus species, with A. fumigatus being the most common pathogen.
- Invasive aspergillosis has a mortality rate of ~100% without treatment, while chronic forms have lower mortality (50% vs. <1% for allergic syndromes).
- Diagnostic methods include galactomannan antigen testing, PCR, β -D-glucan assays, and imaging (e.g., CT for halo signs).
- Treatment for invasive aspergillosis prioritizes voriconazole, itraconazole, or posaconazole, with surgical intervention for fungal balls or localized infections.
- Chronic pulmonary aspergillosis is often mistaken for tuberculosis and requires long-term antifungal therapy ( ≥ 12 months).
1. DEFINITION & OVERVIEW¶
Aspergillosis is a collective term for diseases caused by Aspergillus species, including invasive, chronic, and allergic forms. A. fumigatus is the primary pathogen for invasive and chronic infections, while A. flavus and A. niger are implicated in allergic and localized infections. The disease spectrum ranges from acute invasive infections to chronic granulomatous sinusitis and allergic syndromes.
Table 223-1: Disease Frequency and Diagnostic Sensitivity for Different Manifestations of Aspergillosis¶
| PARAMETER | INVASIVE | CHRONIC | ALLERGIC |
|---|---|---|---|
| Incidence/100,000a | 27.6 | 23.6 | ?b |
| Prevalence/100,000a | — | 55.4 | 286c |
| Global burdena | ~2,116,000 | ~6,141,000 | ~11,690,000 |
| Mortality rate without treatmenta | ~100% | ~50% | <1% |
Table 223-2: Major Manifestations of Aspergillosis¶
| ORGAN | TYPE OF DISEASE |
|---|---|
| Lung | Angioinvasive (in neutropenia), nonangioinvasive, granulomatous |
| Brain | Abscess, hemorrhagic infarction, meningitis |
| ORGAN | TYPE OF DISEASE |
|---|---|
| Sinus | Acute invasive |
| Skin | Acute disseminated, locally invasive (trauma, burns, IV access) |
| Heart | Endocarditis (native or prosthetic), pericarditis |
| Eye | Keratitis, endophthalmitis |
1.1 Disease Types¶
Invasive aspergillosis (IA): Acute or subacute, most common in immunocompromised patients. Chronic pulmonary aspergillosis (CPA): Cavitary lung lesions, often in patients with prior TB or COPD. Allergic bronchopulmonary aspergillosis (ABPA): Hypersensitivity reaction in asthma or CF. Allergic fungal sinusitis (AFS): Chronic sinus inflammation with eosinophilia.
2. EPIDEMIOLOGY¶
Aspergillosis is globally distributed, with high incidence in immunocompromised patients (e.g., neutropenia, HIV, organ transplant recipients). Invasive aspergillosis (IA) incidence is 27.6/100,000, while chronic pulmonary aspergillosis (CPA) prevalence is 55.4/100,000. Allergic fungal sinusitis (AFS) is common in Southeast Asia. Risk factors include prolonged glucocorticoid use, diabetes, and environmental exposure to mold.
2.1 Geographic Variations¶
Chronic granulomatous sinusitis is rare outside the Middle East and India. Fungal keratitis is prevalent in Southeast Asia. Allergic bronchopulmonary aspergillosis (ABPA) is more common in patients from the Indian subcontinent.
3. ETIOLOGY & PATHOPHYSIOLOGY¶
Aspergillus species (e.g., A. fumigatus, A. flavus, A. niger) cause disease via inhalation of conidia. Invasive infection occurs in immunocompromised hosts, while allergic syndromes result from immune hypersensitivity. Genetic factors (e.g., CGD, CFTR mutations) predispose to chronic forms. Pathogenesis involves fungal hyphal invasion, immune evasion, and inflammatory responses.
3.1 Species-Specific Pathogenesis¶
A. fumigatus: Primary cause of IA and CPA. A. flavus: Common in sinus infections and keratitis. A. niger: Causes invasive disease with poor prognosis. A. terreus: Resistant to isavuconazole. A. nidulans: Rare, associated with CGD.
4. CLINICAL FEATURES¶
Invasive aspergillosis presents with fever, cough, hemoptysis, and respiratory distress. Chronic pulmonary aspergillosis (CPA) features cavitary lung lesions, weight loss, and hemoptysis. Allergic bronchopulmonary aspergillosis (ABPA) causes wheezing, eosinophilia, and recurrent pneumonia. Allergic fungal sinusitis (AFS) presents with chronic sinusitis and nasal polyps.
4.1 Imaging Findings¶
CT scans show halo signs (hemorrhagic infarction), nodules, or cavitary lesions. MRI is critical for cerebral aspergillosis. Pulmonary nodules with ground-glass opacities are common in IA.
5. DIFFERENTIAL DIAGNOSIS¶
Invasive aspergillosis must be differentiated from bacterial pneumonia, tuberculosis, and other fungal infections (e.g., cryptococcosis). Chronic pulmonary aspergillosis mimics tuberculosis or lung cancer. Allergic syndromes overlap with asthma, cystic fibrosis, or hypersensitivity pneumonitis.
5.1 Key Differentiators¶
IA: Fever, radiographic halo signs, and positive antigen/PCR. CPA: Cavitary lung lesions with prior pulmonary disease. ABPA: Eosinophilia, IgE elevation, and bronchial obstruction. AFS: Chronic sinusitis unresponsive to antibiotics.
6. INVESTIGATIONS & DIAGNOSIS¶
Diagnostic tests include galactomannan antigen (respiratory samples), β -D-glucan, PCR, and cultures. Imaging (CT/MRI) is essential for localization. Serologic tests (IgE, skin prick) confirm allergic syndromes. Histopathology reveals fungal hyphae in invasive cases.
Respiratory Diagnostic Sensitivity¶
| TEST | INVASIVE | CHRONIC | ALLERGIC |
|---|---|---|---|
| Culture | (cid:214) | (cid:214)-(cid:214)(cid:214) | (cid:214)-(cid:214)(cid:214) |
| Antigen | (cid:214)(cid:214)(cid:214) | (cid:214)(cid:214) | ? |
| Microscopy | (cid:214) | (cid:214) | (cid:214) |
Blood Diagnostic Sensitivity¶
| TEST | INVASIVE | CHRONIC | ALLERGIC |
|---|---|---|---|
| Culture | x | x | x |
| b-D-Glucan | (cid:214)(cid:214) | (cid:214) | ? |
| IgG antibody | (cid:214)(cid:214) | (cid:214)(cid:214)(cid:214) | (cid:214)(cid:214)(cid:214) |
6.1 Diagnostic Algorithms¶
- Suspect IA in immunocompromised patients with fever and radiographic abnormalities. 2. Use antigen/PCR for rapid confirmation. 3. Confirm with histopathology or culture. 4. Serologic tests for ABPA/AFS (IgE, skin prick).
7. MANAGEMENT & TREATMENT¶
Antifungal therapy (voriconazole, itraconazole, posaconazole) is first-line for invasive aspergillosis. Chronic pulmonary aspergillosis requires long-term azoles ( ≥ 12 months). Surgical resection is indicated for fungal balls or localized infections. Corticosteroids are contraindicated in CPA unless antifungal therapy is adequate.
7.1 Treatment Algorithms¶
- IA: Voriconazole (IV/PO) ± surgical debridement. 2. CPA: Long-term azoles ( ≥ 12 months). 3. ABPA: Voriconazole + corticosteroids. 4. AFS: Surgical removal of fungal balls + antifungals.
8. PROGNOSIS & COMPLICATIONS¶
Invasive aspergillosis has a high mortality rate (100% without treatment). Complications include cerebral aspergillosis, hemoptysis, and disseminated infection. Chronic forms may lead to fibrosis or respiratory failure. Corticosteroid use increases mortality in CPA.
8.1 Prognostic Factors¶
Early diagnosis, immune status, and response to antifungals. Cerebral aspergillosis has poor outcomes. Relapse is common in ABPA/SAFS without immune suppression.
9. SPECIAL CONSIDERATIONS¶
Pregnancy: Avoid corticosteroids in CPA. Pediatrics: ABPA in CF or asthma. Elderly: Higher risk of IA due to comorbidities. Immunocompromised patients (e.g., transplant recipients, HIV) require prophylaxis. Drug interactions (e.g., azoles with anticoagulants).
9.1 Drug Interactions¶
Azoles (voriconazole, itraconazole) interact with CYP3A4 substrates (e.g., warfarin, cyclosporine). Monitor drug levels and adjust dosages accordingly.
10. KEY POINTS & CLINICAL PEARLS¶
- Early diagnosis is critical for IA; use antigen/PCR in ICU patients. 2. Avoid corticosteroids in CPA unless antifungal therapy is effective. 3. Surgical intervention is key for fungal balls or localized infections. 4. Monitor for drug resistance (e.g., azole-resistant A. fumigatus). 5. ABPA/SAFS require long-term azole therapy and immune monitoring.