Invasive aspergillosis
Summary
Invasive aspergillosis is a life-threatening fungal infection caused by Aspergillus species (most commonly A. fumigatus) that invades pulmonary vasculature and disseminates in immunocompromised hosts, especially neutropenic patients and transplant recipients. It classically presents with fever, cough, chest pain, and hemoptysis unresponsive to antibiotics. Diagnosis relies on serum/BAL galactomannan, (1,3)-beta-D-glucan, and characteristic CT findings, with voriconazole as first-line treatment.
Detail
Aspergillus is a ubiquitous, septate, acutely branching (45-degree angle) mold found in soil and decaying organic matter. Invasive aspergillosis occurs when inhaled conidia evade normal mucociliary clearance and alveolar macrophage/neutrophil defenses, allowing hyphal invasion of pulmonary blood vessels (angioinvasion). This leads to hemorrhagic infarction, thrombosis, and hematogenous dissemination to the brain, skin, and other organs.
Pathophysiology: The fungus's angioinvasive nature causes vascular thrombosis and tissue necrosis. Key risk factors include prolonged neutropenia (e.g., post-chemotherapy, especially AML induction), hematopoietic stem cell or solid organ transplantation, high-dose corticosteroids, and advanced HIV/AIDS. Chronic granulomatous disease patients are also at risk due to defective NADPH oxidase-mediated killing.
Clinical presentation: Classic triad includes fever refractory to broad-spectrum antibiotics, pleuritic chest pain, and hemoptysis in a neutropenic patient. CNS involvement can cause stroke-like symptoms or brain abscesses due to septic emboli.
Diagnosis: Chest CT may show the 'halo sign' (ground-glass opacity surrounding a nodule, indicating hemorrhage) early in disease, and the 'air-crescent sign' (crescent-shaped air lucency) during neutrophil recovery as the infarcted tissue retracts. Serum galactomannan antigen (cell wall component) and (1,3)-beta-D-glucan assays aid diagnosis. Definitive diagnosis requires histopathology showing septate hyphae with acute-angle branching plus culture confirmation from a sterile site or biopsy.
Treatment: Voriconazole is first-line therapy; alternatives include isavuconazole, amphotericin B (liposomal), or echinocandins (as salvage or combination therapy). Reversal of immunosuppression when possible (e.g., filgrastim for neutropenia) is critical adjunctive management.
Distinguish from allergic bronchopulmonary aspergillosis (ABPA, a hypersensitivity reaction in asthma/cystic fibrosis patients) and aspergilloma (fungus ball in a pre-existing lung cavity, e.g., old TB cavity), which are non-invasive presentations with different management.
Sources
- First Aid for the USMLE Step 1
- Harrison's Principles of Internal Medicine
- UpToDate: Invasive Aspergillosis
- Sabatine's Pocket Medicine
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