aspergillosis
ASPERGILLOSIS
Aspergillosis encompasses a variety of clinical syndromes depending on host immunity factors.
It is caused by Aspergillus, an ubiquitous, soil-dwelling, filamentous fungus that grows on soil, food, dead leaves, household dust, etc. It grows best at 37ºC and the small spores are easily inhaled and deposited deep in the lungs.
The most common pathogens are Aspergillus fumigatus, A. flavus, A. niger and A. terreus.
Aspergilloma is a conglomeration of intertwined Aspergillus hyphae, fibrin, mucus and cellular debris within a pulmonary cavity or an ectatic bronchus.

Aspergillosis Diagnosis

Diagnosis

Invasive Aspergillosis (IA)

  • Standard procedures to establish a diagnosis of IA include: Bronchoalveolar lavage, transthoracic percutaneous needle aspiration or video-assisted thoracoscopic biopsy
    • Fluid and tissue specimens from these reveal angular, dichotomously branching, septate hyphae on direct microscopic examination and/or Aspergillus on culture that confirms diagnosis
    • Biopsy is used as an alternative to bronchoscopy
      • Biopsy with or without polymerase chain reaction (PCR) or galactomannan testing may be an option in severely immunocompromised patients (HSCT or solid organ recipients or with hematological malignancy) highly suspected with IA but with negative Aspergillus PCR test
    • Percutaneous lung biopsy may be attempted for analysis of peripheral nodules
    • Thoracoscopic lung biopsy should be considered when other tests are negative and condition is deteriorating
    • Thrombocytopenia may limit the ability to perform invasive procedures
  • PCR has advantages of rapidity, low cost and ability, as well as sensitivity in establishing diagnosis at the species level
    • Aspergillus PCR testing using blood or serum or bronchoalveolar lavage is recommended in severely immunocompromised patients (HSCT or solid organ transplant recipients or with hematological malignancy) suspected with IA

Allergic Bronchopulmonary Aspergillosis (ABPA)

  • ABPA is difficult to diagnose since it may manifest as bronchial asthma with transient pulmonary infiltrates
  • Aspergillus skin test is recommended for routine screening of all patients with asthma
  • The presence of 7 of the below diagnostic criteria makes the diagnosis of ABPA almost certain
    • Asthma - episodic bronchial obstruction
    • Peripheral eosinophilia (1000 cells/microL)
    • Immediate skin (scratch test) reactivity to Aspergillus antigen
    • Elevated serum immunoglobulin E (IgE) concentrations
    • Serum precipitins to A fumigatus - precipitating antibodies to Aspergillus antigen
    • History of pulmonary infiltrates (transient or fixed)
    • Central bronchiectasis - Irreversible pulmonary damage may occur if treatment is withheld until bronchiectasis develops
  • Secondary diagnostic criteria include:
    • Repeated detection of Aspergillus in sputum samples using stain and/or culture
    • History of expectoration of brown plugs or flecks
    • Elevated specific IgE concentration directed against Aspergillus antigen
    • Arthus reaction (late skin reactivity) to Aspergillus antigen

Allergic Aspergillus Sinusitis (AAS)

  • May occasionally manifest as proptosis due to extension of fungal sinusitis into the orbit

Diagnostic Criteria

  • Sinusitis of ≥1 paranasal sinus on X-ray film
  • Necrosed amorphous tissue along with edematous polyps infiltrated with eosinophils on histopathological evaluation of material from the sinus
  • Demonstration of fungal elements in nasal discharge or in material obtained at the time of surgery by gram stain or culture
  • Absence of diabetes, previous or subsequent immunodeficiency disease and treatment with immunosuppressive drugs
  • Absence of invasive fungal disease at the time of diagnosis or subsequently
  • Other features
    • Peripheral blood eosinophilia
    • Type I and type III cutaneous hypersensitivity to Aspergillus
    • Precipitating antibodies to Aspergillus antigens
    • Elevated total and Aspergillus-specific IgE levels

Aspergilloma 

  • Serum precipitins which are positive for an Aspergillus sp
    •  >95% sensitivity for aspergilloma but may be negative in patients receiving corticosteroids
    •  Usually employed together with chest X-rays to make a diagnosis

Chronic Pulmonary Aspergillosis (CPA)

  • Diagnostic criteria requires the following:
    • Chronic pulmonary symptoms (fever, cough with or without hemoptysis, dyspnea, fatigue, chest pain, sputum production, weight loss) of at least 3 months’ duration
    • Chest radiograph showing infiltrative process
    • Adjacent pleural thickening is a characteristic finding and may be an early indication of a locally invasive process
    • Elevated Aspergillus IgG antibody test
    • Immunosuppression minimal to absent (negative for HIV infection, no history of chemotherapy or immunosuppressive therapy)
  • Histologic demonstration of tissue invasion and growth of Aspergillus on a culture (chronic inflammation, necrosis, fibrosis and/or granulomas, with hyphae in the cavities or superficially adjacent or necrotic tissue, pleural thickening or intracavitary fungus balls) and positive PCR assay for Aspergillus support diagnosis
  • CCPA is characterized by new and/or expanding cavities with thin or thick walls, with pleural thickening and extensive parenchymal destruction and/or fibrosis in patients with chronic lung disease
    • Intracavitary fungal ball may be present

Cutaneous Aspergillosis

  • Presence of hyphae invading blood vessels of the dermis and subcutaneous tissues in skin biopsy is confirmatory

Physical Examination

Otic Aspergillosis

  • The external auditory canal usually contains desquamated epithelial debris and the mold growing on cerumen
    • A niger forms a black tuft while infections due to A fumigatus appear greenish

Laboratory Tests

Histology

Chronic Pulmonary Aspergillosis (CPA)

  • Histologic demonstration of tissue invasion and growth of Aspergillus on a culture (chronic inflammation, necrosis, fibrosis and/or granulomas, with hyphae in the cavities or superficially adjacent or necrotic tissue, pleural thickening or intracavitary fungus balls) and positive PCR assay for Aspergillus support diagnosis

Cutaneous Aspergillosis

  • Presence of hyphae invading blood vessels of the dermis and subcutaneous tissues in skin biopsy is confirmatory

Otic Aspergillosis

  •  Diagnosis can be established with smears demonstrating hyphae

Biomarkers

Invasive Aspergillosis (IA)

  • Use of biomarkers (eg serum and bronchoalveolar lavage galactomannan, (1-3)-β-D-Glucan) may be considered in patients at risk for IA
    • Serum galactomannan testing is recommended in severely immunocompromised patients (with neutropenia, hematologic malignancy, HSCT or solid organ transplant recipients) with unexplained pulmonary infiltrates and suspected with IA
    • Bronchoalveolar lavage testing with galactomannan is recommended in patients with strong risk factors for IA including patients with negative serum galactomannan or positive serum galactomannan but with confounding factors for false-positive results
    • Not recommended for patients currently undergoing antifungal treatment or prophylaxis
  • Antifungal susceptibility testing for Aspergillus isolates is recommended for patients with IA in regions with known resistance to azole drugs or in patients not responding to antifungal therapy

Imaging

Invasive Aspergillosis (IA)

Chest X-ray

  • Air crescent sign in chest radiography can be suggestive but not pathognomonic

Thoracic computed tomography (CT) scan

  • Halo sign which is highly suggestive in patients with compatible host factors
  • Nodule is the earliest sign
  • Focal pulmonary infiltrates
  • Wedge-shaped densities resembling infarcts
  • Contrast media may be used in the presence of a nodule or mass in close proximity to a large vessel
  • Preferred modality for patients at risk for IA and with clinical symptoms of lower respiratory tract infection despite antibacterial therapy or fever of unknown origin
  • Pulmonary CT angiography is recommended in patients with hemoptysis

Allergic Aspergillus Sinusitis (AAS)

Paranasal Computed Tomography (CT) Scan

  • Radiologic evidence of sinusitis can be found in many patients with ABPA
  • Reveals hyperattenuating mucus and/or bony erosion
  • Characteristic feature is the presence of heterogeneous densities signifying opacification of the sinuses, with serpiginous areas of increased attenuation on non-contrast scans

Aspergilloma

Chest X-ray

  • Appears as a solid rounded mass in the upper lobe, mobile, intracavitary mass with an air crescent in the periphery
  • Adjacent pleura may be thickened that is highly characteristic

Computed Tomography (CT) scan

  • CT scan may be necessary to see the aspergilloma more clearly

Chronic Pulmonary Aspergillosis (CPA)

Chest X-ray

  • Chest radiograph shows an infiltrative process in the upper lobes or the superior segments of the lower lobes
    • Adjacent pleural thickening is a characteristic finding and may be an early indication of a locally invasive process
  • Presence of fungal ball on chest imaging requires positive test for Aspergillus IgG or precipitins to confirm diagnosis of CPA
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