Subacute invasive pulmonary aspergillosis

Last revised by Daniel J Bell on 29 May 2023

Subacute invasive pulmonary aspergillosis (previously known as chronic necrotizing aspergillosis or semi-invasive aspergillosis) is subacute to chronic localized and indolent form of invasive aspergillosis. It is also sometimes grouped under the term chronic pulmonary aspergillosis.

This form typically occurs in patients with a depressed immune system, but not as profoundly immunocompromised as bone marrow patients who more frequently develop angioinvasive aspergillosis. Patients are typically middle-aged. Risk factors, therefore, include 1-3:

  • corticosteroids - most common systemic immunodepressant 3

  • diabetes mellitus

  • alcoholism

  • chronic liver disease

  • malnutrition

  • connective tissue diseases such as rheumatoid arthritis and ankylosing spondylitis

  • pre-existing pulmonary pathology - present in ~80% of patients 3

  • advanced age

Typically patients present with progressive respiratory and constitutional symptoms (often for few months) including fever, weight loss, cough, sputum production and hemoptysis 2-3.

Diagnosis is not always straightforward, as both bronchial washings and biopsy have a low diagnostic yield 3.

Although the end result in this form is similar to an aspergilloma, it represents a different process. Rather than Aspergillus colonizing a pre-existing cavity, in CNA a focally invasive aspergillosis occurs which eventually undergoes central necrosis and cavitation forming its own cavity. It is the finding of tissue invasion that allows this entity to be distinguished from the more common aspergilloma 2,5.

The presence of calcium oxalate crystals suggests that Aspergillus niger is the causative agent 3.

The vast majority of patients have positive serum immunoglobulins (Ig)G antibodies to A. fumigatus 7.

Radiographic appearance varies according to when the condition is imaged. It typically involves the upper zones and begins as a pulmonary opacity. Eventually, the central necrotic area separates away from the surrounding lung and thus forms an air crescent sign. This occurs in weeks to months, eventually resulting in a cavity with or without a central mycetoma 3. Appearances may then be the same as an aspergilloma. Often there are multiple cavities, often thick-walled 2. Adjacent pleural thickening is often present 2-3.

It is similar in appearance to tuberculosis, actinomycosis, and histoplasmosis 2.

The condition usually runs a slowly progressive course over weeks to months, and vascular invasion or dissemination to other organs is unusual. 

During initial phases of the disease, antifungals are the mainstay of treatment. Intravenous and intracavitary amphotericin B, 5-flucytosine (5-FC) and itraconazole have all been tried 3

Surgery is reserved for patients who do not respond to initial medical management and have an adequate pulmonary reserve and acceptable operative risks 3,5.

Once the disease has ceased progressing treatment is the same as that of an aspergilloma 1.

Prognosis is largely dictated by underlying lung disease and co-morbidities with mortality ranging from < 10% to 39% depending on criteria for diagnosis and treatment administered 3.

It was first described by Gefter et al. and Binter et al. in 1981 7.

Possible imaging differential considerations include:

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