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Updated: Dec 27 2021


  • Snapshot
    • A 47-year-old man presents to the emergency room with 2 months of fevers, cough, and night sweats. He also reports having hemoptysis. His past medical history of significant for tuberculosis which was adequately treated 2 years ago. He recently tested negative for tuberculosis during routine testing for work which is in the healthcare industry. A chest radiograph shows a cavitary lesion in the left upper lobe. A CT scan further demonstrates a round mobile mass. Fine needle aspiration reveals fungal hyphae along with inflammatory cells. (Aspergilloma)
  • Introduction
    • Classification
      • Aspergillus species
        • Aspergillus fumigatus most commonly causes disease in humans
        • monomorphic fungus with septate hyphae that branch at acute angles (45 degrees)
        • clinical syndromes
          • invasive aspergillosis
            • invasive infection of the lung
            • seen in neutropenic and other immunocompromised patients
          • aspergilloma
            • mycetoma (“fungal ball”) in pre-existing cavity
            • non-invasive
          • allergic bronchopulmonary aspergillosis (ABPA)
            • hypersensitivity reaction in patients with cystic fibrosis or asthma
            • causes bronchiectasis and eosinophilia
            • non-invasive
        • found in soil and decomposed material
        • transmission via inhalation of spores
    • Associated conditions
      • hepatocellular carcinoma from aflatoxins that Apsergillus produce
  • Epidemiology
    • Risk factors
      • immunocompromised status
      • neutropenia
      • steroids or cytotoxic drugs
      • hematologic malignancy
      • chronic granulomatous disease
      • asthma
      • pre-existing lung disease
    • Pathogenesis
      • in patients with competent immune systems, immune system will clear any Aspergillus spores before it can germinate
      • invasive aspergillosis
        • in immunocompromised patients, spores will germinate and produce invasive hyphal structures
      • ABPA
        • local inflammatory reaction can cause an allergic response
  • Presentation
    • Invasive aspergillosis
      • persistent fever
        • neutropenic patients may present with fever only
      • cough with hemoptysis
      • shortness of breath
      • chest pain
    • Aspergillomas
      • cough with hemoptysis
    • Allergic bronchopulmonary aspergillosis (ABPA)
      • new or worsening cough with hemoptysis
      • shortness of breath
      • brownish black mucus plugs in expectorate
      • asthma exacerbations (wheezing)
  • Imaging
    • Chest radiography
      • indication
        • all patients
      • findings
        • aspergilloma
          • round or ovoid mass, often mobile
    • Chest computed tomography (CT)
      • indication
        • all patients
      • findings
        • invasive aspergillosis
          • nodules with halo sign (rim of ground glass opacity)
          • cavitary lesions
        • aspergilloma
          • well-formed cavitary lesion, often mobile (changes as the patient changes position)
          • Monad sign
            • air surrounding soft tissue mass, indicating pre-existing cavity
        • ABPA
          • bronchiectasis
    • Bronchoscopy
      • indication
        • to obtain sample for culture or pathology
        • invasive aspergillosis
      • findings
        • tracheobronchial ulceration
        • nodules
        • pseudomembranes or plaques
  • Studies
    • Labs
      • detection of Aspergillus galactomannan antigen in serum, bronchoalveolar lavage fluid, or cerebrospinal fluid
      • eosinophilia and elevated IgE in those with ABPA
    • Biopsy of affected tissue
      • hyphae invasion into tissue
    • Culture of sterilely-obtained sample
      • positive culture
    • Making the diagnosis
      • invasive aspergillosis
        • definitive diagnosis of invasive aspergillosis requires either
          • pathologic examination with invasive hyphae in tissue
          • positive Aspergillus culture
      • ABPA
        • based on clinical findings and eosinophilia or elevated IgE
      • aspergilloma
        • abnormal sputum culture or positive culture or serology
        • aspergilloma seen on imaging
  • Differential
    • Pneumocystis pneumonia
      • distinguishing factors
        • hemoptysis is rare
        • often presents as progressive exertional shortness of breath
        • CT imaging shows bilateral and diffuse patchy ground-glass opacities
    • Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)
      • distinguishing factor
        • often involves other organ systems, including skin, cardiac, gastrointestinal, and renal
  • Treatment
    • Medical
      • steroids
        • indications
          • first-line
          • ABPA
      • voriconazole
        • indications
          • first-line
          • invasive aspergillosis
      • caspofungin
        • indications
          • contraindication to voriconazole
          • invasive aspergillosis
      • amphotericin B
        • indication
          • often used as adjuvant therapy with voriconazole
          • invasive apsergillosis
    • Operative
      • surgical resection
        • indication
          • aspergilloma
  • Complications
    • Disseminated infection
    • Vascular invasion
  • Prognosis
    • Invasive aspergillosis
      • can have high mortality (> 60%) in severely immunocompromised patients
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