Aspergillosis

Background

Aspergillus is a fungus (mould) that is found in abundance throughout the environment in soil, decomposing plant matter, ornamental plants, water, household dust, and building materials. More than 100 different species of Aspergillus have been identified, but the species most commonly implicated in human disease are A fumigatus, A flavus, and A niger.

Most people breathe in Aspergillus spores every day, with no ill-effect. However, in patients with pre-existing medical conditions Aspergillus can cause disease, primarily lung infection. Infection is more likely if a large number of spores are inhaled, such as exposure to a very dusty environment or building renovation. Although Aspergillus most commonly enters the human body via inhalation, on rare occasions the fungus may enter via the skin (primary cutaneous aspergillosis), particularly in patients with thermal burns or trauma. Occasionally outbreaks of primary cutaneous aspergillosis can occur due to contaminated biomedical equipment.

Clinical features

There are four common clinical patterns of disease.

Pattern of disease	Clinical features	Population at risk
Acute invasive aspergillosis	Rapid onset and short progression of disease. Fungus invades and damages body tissues; most commonly the lungs and/or sinuses, but can spread throughout the body via the bloodstream. Symptoms include fever, cough, breathlessness, chest pain, facial swelling, bleeding nose, bulging of an eye, or neurological symptoms. Other symptoms develop if infection spreads beyond the lungs and sinuses. High fatality rate.	People with severely impaired immunity, particularly those: who have had a bone marrow transplant or solid organ transplant on high doses of corticosteroids or chemotherapy for cancers such as leukaemia with advanced HIV infection
Allergic aspergillosis	Allergic reaction in lungs and/or sinuses. Lung symptoms include fever, wheezing, and coughing. Patients may cough up blood or mucous plugs. Sinus symptoms include facial pressure, headache, blocked nose, yellow or green discharge from the nose, and cough.	Can affect anyone, but more common in people with asthma or cystic fibrosis.
Aspergilloma	Aspergilloma is a “fungus ball” that develops in a pre-existing lung cavity. May have no symptoms or may cough up blood (can be profuse and life-threatening). Aspergillomas can also develop in other organs.	People with underlying cavity-causing lung disease, such as tuberculosis, emphysema, or cystic fibrosis.
Chronic necrotising (causing tissue death) pulmonary aspergillosis	Slowly progresses over weeks or months. Symptoms include fever, cough, night sweats, and weight loss. Rare condition.	People with mild immune impairment, such as underlying lung disease, alcoholism, or long-term corticosteroid therapy.

Aspergillosis is becoming more common as conditions producing impaired immunity become more prevalent. For example, invasive aspergillosis is estimated to occur in 5-13% of recipients of bone marrow transplants, 5-25% of patients who have received heart or lung transplants, and 10-20% of patients who are receiving intensive chemotherapy for leukaemia.

Skin manifestations

Skin changes most commonly occur as a consequence of widespread infection with Aspergillus in patients with impaired immunity.

• Around 5-10% of patients with invasive aspergillosis develop skin lesions.
• Lesions include single or multiple red or violet hardened plaques (broad flat lesions) or papules (small bumps). The lesions may be tender or symptom-free. As the lesions evolve, pus- or blood-filled blisters develop in the centre, which eventually become necrotic (blackened due to death of tissue) ulcers or scabs. Lesions most commonly appear on the limbs and head, and may affect a small or large area.

Clinical features of primary cutaneous aspergillosis:

• Primary cutaneous aspergillosis most commonly develops at the site of an intravenous cannula insertion or venipuncture (wound from a blood test). Occlusive dressings may increase the risk of developing this condition.
• Lesions initially appear as a cellulitis, then develop into a necrotic ulcer or scab as above.

The term aspergillosis is not used to refer to chronic nail infections (onychomycosis) caused by Aspergillus, which may affect people with normal immune systems.

Cutaneous aspergillosis

Diagnosis

• Samples of sputum, blood, or affected tissue can be cultured in the laboratory to grow Aspergillus.
• The fungus may be visible under a microscope in biopsies of affected tissue. Special stains for fungus may be needed, but other fungi may appear nearly identical.
• Chest x-ray or CT scan of the lungs can reveal characteristic abnormalities.
• A newer antigen-based test is available to detect evidence of invasive aspergillosis in the blood. However, accuracy of this test appears to be variable.

Potassium hydroxide stain of Aspergillus in culture

Treatment

• Voriconazole is currently used as first-line treatment for invasive aspergillosis.
• Alternatives include itraconazole, amphotericin B, caspofungin, micafungin, and posaconazole.
• Prolonged treatment is usually required.
• When possible, immunosuppressive therapy, such as corticosteroids, should be discontinued.
• Surgical removal of the infected lung cavity may be required for aspergillomas.

Prevention

Because this fungus is present everywhere throughout the environment it is virtually impossible to avoid it altogether. In patients with severely impaired immunity, the following measures may be helpful:

• Avoid dusty environments, construction sites, gardening, and lawn mowing.
• Wear protective face masks when near dusty environments.
• Preventative antifungal medication may be useful.
• High-efficiency particulate air filters (HEPA) can be used in hospitals to prevent hospital-acquired lung infections in patients with poor immunity.

Draft 5 April 2010