The patient was clear that their inhalers weren’t working very well to control their symptoms and that whilst they had had some response from the steroids a previous GP had recommended the response hadn’t lasted; within a few days of stopping they were just as bad as before. On further questioning the GP found out that a couple of months ago the patient had sold their house and moved in to an old cottage which they were renovating. There had been lots of brick dust around and the GP started to wonder if this might be relevant to the patient’s illness.
The GP called the Microbiologist, who advised blood tests to look for antibodies against A. fumigatus as well as a chest x-ray. The patient was restarted on steroids whilst awaiting the results and a follow up appointment for a week’s time was organised, along with a referral to the Respiratory Physicians for ongoing management and follow-up as these specialists would normally manage these types of fungal infection.
What is aspergillosis?
Aspergillosis is the terms used for any infection caused by one of the Aspergillus spp. There are five main species that infect humans:
1. Aspergillus fumigatus (most common)
2. Aspergillus flavus
3. Aspergillus terreus
4. Aspergillus niger
5. Aspergillus nidulans
These fungi are moulds that produce fluffy colonises when growing in the environment or in the laboratory. They produce spores, which are the infectious component that can be inhaled leading to infection. Because of this route of transmission, by far the most common type of aspergillosis is pulmonary aspergillosis. Infection can occur when spores settle in wounds, are introduced accidently during surgery (e.g. into the eye), are ingested and settle in the gut, or disseminate or spread from adjacent sinuses to cause brain abscesses. However, infection is uncommon and occurs in specific at risk patients; hence aspergillosis is considered an opportunistic infection.
How does pulmonary aspergillosis present?
The three most common presentations of pulmonary aspergillosis:
1. Invasive pulmonary aspergillosis (IPA)
2. Allergic bronchopulmonary aspergillosis (ABPA)
IPA is the most acute and usually the most severe type of infection. In this situation the fungus invades along blood vessels (angioinvasive) causing tissue destruction, necrosis and pulmonary haemorrhages. The patient usually presents with a cough, fever, shortness of breath, chest pain and haemoptysis. IPA usually occurs in patients with impaired immunity either due to haematological cancer, chemotherapy, immunomodulation with steroids or anti-organ rejection drugs and congenital immunodeficiencies. If these patients inhale the spores of the Aspergillus spp. and fail to clear them by coughing then they can invade and establish an infection.
ABPA occurs when a person is chronically colonised with Aspergillus fumigatus in their respiratory tract and then develops an allergic response to the fungus. This chronic allergic response leads to inflammation, tissue damage and fibrosis. ABPA usually presents with a recurrent asthma like illness but fever, cough, haemoptysis and nasal discharge can also occur. The main factor that suggests ABPA rather than IPA is the chronic and recurrent picture rather than the acute and fulminant nature of IPA. ABPA is more common in patients with a pre-existing lung condition such as asthma or cystic fibrosis.
An aspergilloma is essentially a ball of fungus containing Aspergillus spp. The fungal ball usually occurs in an already damaged portion of lung, e.g. in patients with chronic obstructive pulmonary disease, pulmonary fibrosis or an old tuberculosis scar. Patients with aspergillomas can either be asymptomatic (the fungal ball is noted coincidentally when looking for another diagnosis) or they may present with a history of many months of weight loss, cough, night sweats, fatigue and occasionally haemoptysis. Usually there is a the background of a different chronic lung condition.
How is pulmonary aspergillosis diagnosed?
The key to diagnosing aspergillosis is clinical suspicion! If you don’t think about it, you won’t diagnose it. Aspergillosis is often diagnosed in patients at risk who have failed to respond to more conventional antibacterial therapy. Remember that’s because antibiotics are antibacterial they are not there to treat viruses or fungi!
Diagnostic tests for aspergillosis can be split into microbiology, histopathology and radiology.
The microbiology tests for aspergillosis include microscopy and culture of tissue or pus taken from a normally sterile site e.g. lung, bronchoalveolar lavage or abscess. Sputum can also be cultured but as Aspergillus spp. can be found colonising the respiratory tract without causing infection or allergic response therefore a positive culture may mislead doctors into thinking these colonisers are the cause of the patient’s problems. A positive culture should be backed up with other tests (see below). PCR can also be performed on tissue or pus to detect Aspergillus spp. however PCR has the same drawback as culture in that it cannot distinguish infection from colonisation.
Galactomannan is specific for Aspergillus spp. and has a high positive predictive value up to 80% in high risk patient groups e.g. bone marrow transplant recipients. However neither of these serological tests can diagnose ABPA or aspergilloma, as in these conditions there are no fungal cell wall fragments in the bloodstream; the fungi are either in the airway or contained in a fungal ball.
ABPA is diagnosed by detecting Aspergillus spp. specific IgG and IgE antibodies known as aspergillus precipitins. These patients often have a high total eosinophil count in their peripheral blood but this is not diagnostic and should be used to prompt further investigation for the specific cause.
For further information on the diagnosis of fungal infections and also the role of histopathology and radiology see the previous blog on the British Society for Medical Mycology guidelines.
How is pulmonary aspergillosis treated?
The treatment of pulmonary aspergillosis depends on the type of infection the patient has.
For IPA the mainstay of treatment is Voriconazole. This has been shown to be superior to other antifungals; it also has the benefit of being available orally, allowing an easy IV to oral switch to facilitate the patient going home. The main problem with Voriconazole is that it interacts with a lot of other medications which can often mean it cannot be used. These include treatments the patient may already be on for their underlying immunosuppressing condition such as anticancer drugs or anti-organ rejection drugs. It is crucial that a careful check of the patients other medications is done before starting Voriconazole. Many patients taking Voriconazole also get unpleasant side effects such as visual disturbances (up to 20%), rash (7%), hallucinations and even cardiac and bone damage. Alternative treatments for IPA include Liposomal Amphotericin B (NOT active against A. terreus) or Caspofungin, both of which are intravenous and are NOT as effective as Voriconazole.
ABPA is treated with steroids to control the allergic response and prevent inflammation causing lung damage. Oral Itraconazole is often also given to reduce the duration of steroid therapy and prevent steroid induced side effects.
The treatment of aspergillomas depends on whether the patient is symptomatic or not. Asymptomatic patients require no specific treatment as the treatment is considered to carry a higher risk of patient harm than the presence of the fungal ball. However, symptomatic patients require surgery to remove the fungal ball, in addition to either Itraconazole or Voriconazole. Antifungal treatment alone is not usually effective at treating aspergillomas.
The patient came back to see the GP a week later feeling a bit better. The blood tests and chest x-ray confirmed a diagnosis of allergic bronchopulmonary aspergillosis and the patent was started on Itraconazole. The patient’s appointment with the respiratory physicians came through quickly and they monitored the progress and continued the treatment for 6 months. The patient made a good recovery, although they are still allergic to Aspergillus spp. and may get further flare ups of their ABPA in the future.