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.

Diagnosis

Invasive Aspergillosis (IA)

  • Standard procedures to establish a diagnosis of IA includes: 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
    • 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
  • Polymerase Chain Reaction (PCR) has advantages of rapidity, low cost & ability to establish diagnosis at the species level
    • Very promising but still investigational

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 & type III cutaneous hypersensitivity to Aspergillus
    • Precipitating antibodies to Aspergillus antigens
    • Elevated total & 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

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 & 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

  • 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

  • Use of biomarkers (eg serum and bronchoalveolar lavage galactomannan, (1-3)-β-D-Glucan) may be considered in patients at risk for IA
    • Not recommended for patients currently undergoing antifungal treatment or prophylaxis

Imaging

Invasive Aspergillosis

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

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

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 & may be an early indication of a locally invasive process
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