Aspergillus/Aspergillosis

Aspergillosis is an opportunistic fungal infection caused by Aspergillus species, which are common spore-forming molds found in our environment. As Aspergillus species are opportunistic, they cause disease primarily in patients who are immunocompromised. The organs that are most commonly involved are the lungs and sinuses. Invasive aspergillosis can spread hematogenously and may involve the brain, heart, and skin. Symptoms may vary depending on the organ involved, but pulmonary symptoms may include shortness of breath, wheezing, cough, and hemoptysis. The diagnosis is made based on imaging studies, fungal cultures, and analysis of serologic or respiratory samples. Management depends on the presentation but can include antifungal therapy and surgical resection in severe disease.

Last update:

Table of Contents

Share this concept:

Share on facebook
Share on twitter
Share on linkedin
Share on reddit
Share on email
Share on whatsapp

General Characteristics of Aspergillus

Characteristics:

  • Exists only as a mold (not dimorphic)
  • Highly aerobic
  • Grows on plants, soil, household dust, and food
  • Obtains nutrients from dead and decaying matter
  • Best visualized with silver stains

Morphology:

  • Hyphae
    • Long, filamentous structures
    • Frequent septae 
    • Form dichotomous branches (45-degree angles)
    • Walls are typically parallel
  • Conidia
    • Asexual, nonmotile spores
    • Spherical
    • Originate from conidiophores (specialized hyphal branch)

Clinically relevant species

Over 250 species of Aspergillus exist; however, only the following species are most commonly associated with aspergillosis:

  • A. fumigatus (most common)
  • A. niger
  • A. flavus
  • A. terreus

Forms of aspergillosis

Aspergillosis can have variable clinical presentations, with the most commonly involved organ systems being the lungs and skin. These disease presentations include:

  • Allergic bronchopulmonary aspergillosis (ABPA)
  • Aspergillus sinusitis
  • Aspergilloma
  • Chronic pulmonary aspergillosis
  • Invasive aspergillosis
  • Cutaneous aspergillosis

Epidemiology and Pathogenesis

Epidemiology

Limited statistics are available on aspergillosis.

  • ABPA potentially affects: 
    • 1%–15% of patients with cystic fibrosis
    • 2.5% of patients with asthma
  • Invasive aspergillosis:
    • Uncommon and primarily occurs in immunocompromised individuals 
    • Incidence: 1–2 cases in 100,000 individuals in the United States
      • Higher in patients who have undergone a transplant
      • Associated with approximately 15,000 hospitalizations

Host risk factors

Humans inhale spores daily, but generally do not develop the disease if they have a competent immune system. Aspergillosis often occurs in people with underlying conditions such as:

  • Immunosuppression: 
    • HIV
    • Chemotherapy
    • Hematologic malignancy
    • Chronic steroid use
    • Transplant recipients
  • Lung disease:
    • Tuberculosis 
    • Asthma
    • Cystic fibrosis
    • Chronic obstructive pulmonary disease (COPD)
    • Sarcoidosis
    • Lung cancer

Transmission

  • Inhalation of spores (most common)
  • Invasion through damaged skin

Pathophysiology

The pathogenesis of each type of aspergillosis is not completely understood.

In immunocompetent patients:

  • Inhalation of conidia → taken up by macrophages 
  • Germination into hyphae → immune recognition by cell wall components
  • Neutrophil recruitment → hyphae destruction

In immunocompromised patients:

  • Hyphae invade tissues and walls of blood vessels → invasive aspergillosis
  • The invasion results in the following conditions in organs (most commonly the lung):
    • Tissue infarction
    • Hemorrhage
    • Necrosis 

In patients with underlying lung disease:

  • Tissue invasion is not as common unless concurrent immunodeficiency is present.
  • Aspergillus may inhabit pulmonary cavities → a tangled mass of hyphae, fibrin, and inflammatory cells can develop → aspergilloma (fungus ball)
  • The presence of Aspergillus can trigger a hypersensitivity reaction → ABPA

Clinical Presentation

The clinical presentation varies based on the form of aspergillosis.

Common constitutional symptoms

The following symptoms may be seen with any form of aspergillosis:

  • Fevers
  • Chills
  • Night sweats
  • Weight loss
  • Malaise

Allergic bronchopulmonary aspergillosis

Allergic bronchopulmonary aspergillosis should be suspected in patients with asthma or cystic fibrosis who present with recurrent exacerbations. Symptoms include:

  • Dyspnea
  • Cough:
    • Productive
    • Green or brown mucous plugs
  • Hemoptysis
  • Wheezing

Aspergillus sinusitis

Aspergillus sinusitis may be allergic or invasive. Symptoms include:

  • Nasal congestion
  • Purulent nasal discharge
  • Decreased sense of smell
  • Facial discomfort and/or sinus tenderness
  • Headache

Chronic pulmonary aspergillosis and aspergilloma

Some patients with chronic pulmonary aspergillosis and aspergilloma are asymptomatic. Symptomatic individuals may present with:

  • Chest pain
  • Dyspnea
  • Cough (dry or productive)
  • Hemoptysis
  • Note: Constitutional symptoms often occur with chronic pulmonary aspergillosis but not with aspergilloma.

Invasive aspergillosis

Pulmonary:

  • Fever
  • Cough
  • Hemoptysis 
  • Pleuritic chest pain
  • Respiratory distress

Disseminated infection:

  • Endophthalmitis
  • Endocarditis
  • CNS aspergillosis:
    • Seizures
    • Focal neurologic deficits
    • Mycotic aneurysms → subarachnoid hemorrhage

Cutaneous aspergillosis

Cutaneous aspergillosis may occur from direct inoculation or disseminated infection. Patients may present with:

  • Erythematous lesions with red or violet hardened plaques
  • Indurated or umbilicated papules and nodules
  • An overlying black eschar may occur.
Cutaneous aspergillosis

Cutaneous aspergillosis lesions:
A and B: Nodular lesions
C: Erythema and necrosis of a toe
D: A large necrotic plaque with surrounding erythema on a patient’s chest

Image: “Cutaneous aspergillosis” by Dermatology Department, UPEC (CB, SI-H-O, OC), Paris, France. License: CC BY 4.0

Diagnosis

Imaging

Chest imaging with X-ray or CT are commonly ordered. Findings may include:

  • ABPA: central bronchiectasis and pulmonary opacities
  • Aspergilloma: air crescent sign (a crescent of air around a fungus ball within a cavity)
  • Invasive aspergillosis:
    • Single or multiple nodules → can progress to cavitation
    • Patchy or segmental consolidation
    • “Tree-in-bud” appearance if bronchiolitis present
    • Halo sign: ground-glass opacity around a pulmonary nodule that results from direct invasion into a pulmonary vessel

Laboratory evaluation

  • Tests for invasive aspergillosis:
    • Galactomannan antigen detection:
      • Polysaccharide in Aspergillus cell walls
      • Performed using enzyme immunoassay
    • 1,3 beta-D-glucan:
      • A cell wall component of many fungi
      • Less sensitive than the test to detect galactomannan
  • Evaluation for ABPA may demonstrate: 
    • Eosinophilia
    • Elevated serum IgE levels against Aspergillus
    • Positive skin reactivity to Aspergillus antigen testing
  • Testing for chronic pulmonary aspergillosis: Aspergillus IgG antibody

Culture and histopathology

  • Definitive diagnostic modality
  • Taken from tissue, or fluid sampling of the affected organ
  • The fungus can be identified by methenamine silver staining or periodic acid-Schiff staining.
Histopathology of aspergillosis

Methenamine silver-stained tissue section showing septate hyphae of Aspergillus species

Image: “Histopathology and growth on culture medium” by Department of Orthopaedics, All India Institute of Medical Sciences, New Delhi 110029, India. License: CC BY 4.0

Management and Prevention

Management of ABPA

  • Oral steroids 
  • Itraconazole is reserved for patients who cannot tolerate steroid tapers.
  • Optimize therapy for cystic fibrosis or asthma.

Chronic pulmonary aspergillosis and aspergilloma

  • Aspergilloma does not require therapy if asymptomatic and does not respond to antifungal therapy.
  • Antifungal therapy for chronic pulmonary aspergillosis:
    • Itraconazole
    • Voriconazole
  • Bronchial artery embolization for massive hemoptysis
  • Surgical resection for severe disease

Management of invasive aspergillosis

The following options may be used in invasive disease, including invasive sinusitis, cutaneous disease, and disseminated disease:

  • Antifungal therapy:
    • Voriconazole (preferred)
    • Amphotericin B
    • Caspofungin
  • Management of immunosuppression:
    • Discontinuation of corticosteroids
    • Antiretroviral therapy for HIV
  • Surgical: 
    • Debridement of necrotic tissue
    • Valve replacement for endocarditis

Prevention

  • Posaconazole is most commonly used for prophylaxis in patients who are immunocompromised.
  • Reduce mold exposure (if the source is known).

Differential Diagnosis

  • Coccidioidomycosis: an infection caused by Coccidioides fungi that can present in patients who are immunocompetent or immunocompromised. Coccidioides is known to cause both pulmonary and extrapulmonary disease. Coccidioidomycosis is diagnosed using serology, microscopic examination of specimens, and fungal cultures. Medical treatment is primarily with fluconazole, itraconazole, or amphotericin B (for severe disease).
  • Paracoccidioidomycosis: an opportunistic infection caused by Paracoccidioides. Patients may present with mucocutaneous, lymphatic, or visceral disease. Paracoccidioidomycosis is diagnosed based on microscopic evaluation of specimens and culture. Medical treatment is primarily with itraconazole or amphotericin B (for severe cases).
  • Blastomycosis: a pulmonary disease caused by inhaling the spores of Blastomyces. Patients can develop pneumonia or disseminated extrapulmonary disease. The diagnosis is made with imaging and cultures. If patients do not spontaneously improve, itraconazole may be given. Medical treatment includes fluconazole, itraconazole, or amphotericin B (in severe cases). 
  • Histoplasmosis: an infection caused by Histoplasma capsulatum. Symptoms may be nonspecific or consistent with those of pneumonia. Histoplasmosis is diagnosed based on fungal cultures or urine and serum antigen testing. Itraconazole may be given if patients do not show improvement in symptoms.
  • Cryptococcosis: an opportunistic infection caused by the yeasts, Cryptococcus neoformans or C. gattii. Patients may develop pneumonia, meningitis, or cutaneous disease. Fungal cultures and cryptococcal antigen testing can provide the diagnosis. Management depends on the presentation but can include fluconazole and amphotericin B (for meningitis).

References

  1. Akuthota, P. (2021). Treatment of allergic bronchopulmonary aspergillosis. UpToDate. Retrieved April 19, 2021, from https://www.uptodate.com/contents/treatment-of-allergic-bronchopulmonary-aspergillosis
  2. Aspergillosis. (2020). Retrieved April 19, 2021, from https://www.cdc.gov/fungal/diseases/aspergillosis/index.html
  3. Gaillard, F. (n.d.). Pulmonary aspergillosis: Radiology reference article. Retrieved April 19, 2021, from https://radiopaedia.org/articles/pulmonary-aspergillosis?lang=us
  4. Kauffman, C. (2021). Diagnosis of invasive aspergillosis. UpToDate. Retrieved April 19, 2021, from https://www.uptodate.com/contents/diagnosis-of-invasive-aspergillosis
  5. Patterson, T. (2021). Treat and prevention of invasive aspergillosis. UpToDate. Retrieved April 19, 2021, from https://www.uptodate.com/contents/treatment-and-prevention-of-invasive-aspergillosis
  6. Kauffman, C.A. (2019). Epidemiology and clinical manifestations of invasive aspergillosis. In Bond, S. (Ed.). UpToDate. Retrieved April 23, 2021, from https://www.uptodate.com/contents/epidemiology-and-clinical-manifestations-of-invasive-aspergillosis
  7. Denning, D.W. (2020). Clinical manifestations and diagnosis of chronic pulmonary aspergillosis. In Bond, S. (Ed.). UpToDate. Retrieved April 23, 2021, from https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-chronic-pulmonary-aspergillosis
  8. Akuthota, P., Weller, P.F. (2020). Clinical manifestations and diagnosis of allergic bronchopulmonary aspergillosis. In Hollingsworth, H. (Ed.). UpToDate. Retrieved April 23, 2021, from https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-allergic-bronchopulmonary-aspergillosis
  9. Vuong, M.F., Waymack, J.R. (2020). Aspergillosis. [online] StatPearls. Retrieved April 23, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK482241/
  10. Ortega, V.E., and Genese, F. (2019). Allergic bronchopulmonary aspergillosis (ABPA). [online] MSD Manual Professional Version. Retrieved April 23, 2021, from https://www.msdmanuals.com/professional/pulmonary-disorders/asthma-and-related-disorders/allergic-bronchopulmonary-aspergillosis-abp
  11. Revankar, S.G. (2019). Aspergillosis. [online] MSD Manual Professional Version. Retrieved April 23, 2021, from https://www.msdmanuals.com/professional/infectious-diseases/fungi/aspergillosis

Study on the Go

Lecturio Medical complements your studies with evidence-based learning strategies, video lectures, quiz questions, and more – all combined in one easy-to-use resource.

Learn even more with Lecturio:

Complement your med school studies with Lecturio’s all-in-one study companion, delivered with evidence-based learning strategies.

🍪 Lecturio is using cookies to improve your user experience. By continuing use of our service you agree upon our Data Privacy Statement.

Details