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Aspergillosis

Last updated: January 21, 2021

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Aspergillosis is the collective term for diseases caused by mold species in the genus Aspergillus. Aspergillus spores are ubiquitous but do not usually cause infection in immunocompetent individuals. Risk factors for Aspergillus infection include immunosuppression (e.g., HIV, hematologic malignancies, transplant recipients) and underlying pulmonary conditions (e.g., cavernous tuberculosis, COPD). Infections may be localized, causing asymptomatic pulmonary aspergilloma, or symptomatic, complicated infiltrates (e.g., with cavitation, fibrosis, or necrosis). In immunocompromised patients, invasive aspergillosis is common, which manifests as severe pneumonia and septicemia with potential involvement of other organs. In patients with pre-existing bronchopulmonary conditions (e.g., asthma, cystic fibrosis), Aspergillus may cause allergic bronchopulmonary aspergillosis (ABPA), which presents with asthmatic symptoms or sinusitis. Elevated serum IgE levels and eosinophilia indicate a fungal infection. Tissue biopsy followed by histopathology and culture is used to confirm the diagnosis. Medical treatment for aspergillosis infection includes voriconazole, caspofungin, or amphotericin B. An aspergilloma, on the other hand, must be surgically removed. ABPA is primarily managed with glucocorticoid therapy. Immunocompromised patients should receive prophylactic posaconazole.

Clinical features of aspergillosis
Lung manifestations Other manifestations [2][3]
ABPA [4]
Chronic pulmonary aspergillosis [5]
Invasive aspergillosis [6]

Invasive aspergillosis mostly infects the bronchioles of the lungs, but can also manifest as a disseminated infection (e.g., skin, CNS).

Diagnostics of aspergillosis
Laboratory tests Chest x-ray and CT Tissue biopsy and/or culture
ABPA [4]
  • N/A
Chronic pulmonary aspergillosis [5]
Invasive aspergillosis [6]
  • Positive galactomannan antigen test: Galactomannan antigen is a heteropolysaccharide component of the Aspergillus cell wall that is shed during the phase of hyphal growth.
  • Positive 1,3-β-D glucan test [7]

The most important diagnostics for the different aspergillosis types are:
ABPA: increased IgE and eosinophil count.
Aspergilloma: positive culture or serology and fungus ball seen on chest imaging.
Invasive aspergillosis: positive culture or biopsy showing septate hyphae.

Differential diagnosis of pulmonary fungal infections
Mycoses Etiology Clinical features Diagnosis Treatment

Aspergillosis

Coccidioidomycosis (Valley fever)
Paracoccidioidomycosis
  • KOH/calcofluor staining on smears or silver/PAS-staining on tissue biopsy: budding yeast with “captain's wheel” appearance
  • Cultures have a low sensitivity
Blastomycosis
Histoplasmosis
  • Infected patients often asymptomatic
  • Acute pneumonia
  • Extrapulmonary manifestations (e.g., ulcerative oral lesions)
Cryptococcosis
Candidiasis
Pneumocystis pneumonia

The differential diagnoses listed here are not exhaustive.

Treatment of aspergillosis [3][8][9]
General measures Medical therapy Surgical therapy
ABPA [4]
  • Oral glucocorticoids
  • For acute or recurrent ABPA: itraconazole
Chronic pulmonary aspergillosis [5]
  • Asymptomatic patients without disease progression
    • Do not require treatment
    • Should undergo regular follow-ups (imaging and Aspergillosis antibody titer tests)
  • Aspergilloma
  • Other types: In the case of severe disease, surgical resection may be required.
  • All types: bronchial angiography and embolization for temporary stabilization in the event of massive hemoptysis
Invasive aspergillosis [6]
  • Protective measures: See “Prevention” below.
  • N/A

Prophylactic therapy

Reduction of mold exposure

The following measures reduce the risk of indoor mold exposure according to the CDC guidelines:

  • Protective measures taken at home:
    • Use a ventilation hood while cooking
    • Add mold inhibitors to wall paint
    • Use mold killers in bathrooms
    • Ensure regular ventilation (complete opening of the windows for 5–10 min) and adequate heating (especially in winter) in order to keep the humidity as low as possible.
    • Avoid drying laundry indoors, use of humidifiers, and carpets in bathrooms.
  • Protective measures taken during the construction of buildings, both indoors and outdoors:
    • Adequate insulation
    • Sealing of the floor to prevent moisture from the soil from entering and pervading it
    • Protection from driving rain
    • Regular re-roofing
    • Ensuring the floors and roofs are watertight.
    • Adequate dust cover measures need to be incorporated during construction and restoration work so that there is reduced exposure to the mold present in the dust that is normally stirred up.
  1. Chini BA. Allergic Bronchopulmonary Aspergillosis. Elsevier ; 2007 : p. 15
  2. Aït-Mansour A, Pezzettigotta S, Genty E, Faulcon P, Lecanu JB. Evaluation of the prevalence and specificities of asymptomatic paranasal sinus aspergillosis: Retrospective study of 59 cases. Eur Ann Otorhinolaryngol Head Neck Dis. 2015; 132 (1): p.19-23. doi: 10.1016/j.anorl.2013.10.006 . | Open in Read by QxMD
  3. Information for Healthcare Professionals about Aspergillosis. https://www.cdc.gov/fungal/diseases/aspergillosis/health-professionals.html. Updated: September 7, 2016. Accessed: March 23, 2017.
  4. Patterson K, Strek ME. Allergic bronchopulmonary aspergillosis. Proc Am Thorac Soc. 2010; 7 (3): p.237-244. doi: 10.1513/pats.200908-086al . | Open in Read by QxMD
  5. Denning DW. Clinical Manifestations and Diagnosis of Chronic Pulmonary Aspergillosis. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-chronic-pulmonary-aspergillosis.Last updated: September 8, 2016. Accessed: March 22, 2017.
  6. Kauffman CA. Epidemiology and Clinical Manifestations of Invasive Aspergillosis. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/epidemiology-and-clinical-manifestations-of-invasive-aspergillosis.Last updated: December 22, 2015. Accessed: March 22, 2017.
  7. Fontana C. (1-3)-β-D-glucan vs galactomannan antigen in diagnosing invasive fungal infections (IFIs). Open Microbiol J. 2012; 6 : p.70-73. doi: 10.2174/1874285801206010070 . | Open in Read by QxMD
  8. Limper AH, Knox KS, Sarosi GA et al. An official American Thoracic Society statement: treatment of fungal infections in adult pulmonary and critical care patients. Am J Respir Crit Care Med. 2011; 183 (1): p.96-128. doi: 10.1164/rccm.2008-740ST . | Open in Read by QxMD
  9. Walsh TJ, Anaissie EJ, Denning DW et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2008; 46 (3): p.327-360. doi: 10.1086/525258 . | Open in Read by QxMD