Severe Asthma with Fungal Sensitisation (SAFS)

Some patients with severe asthma (i.e. those requiring oral or high dose inhaled steroids) are sensitised to Aspergillus and/or other fungi. However, they do not have ABPA. This condition is called SAFS (severe asthma with fungal sensitisation), or is sometimes known as “fungal asthma”. The mean age at diagnosis of SAFS is ~50 years old.


Presentation:

Many patients will have significant nasal symptoms, including runny nose, sneezing and hayfever-like symptoms. Chronic persistent asthma symptoms which are poorly controlled by multiple medications is a common feature for SAFS. Admission to hospital for asthma exacerbations is also common. Unlike some ABPA patients, they do not produce plugs of sputum; however, CT scans may show some mucous in airways. Eosinophilia is common. Their pulmonary function measured by FEV1 or peak flow varies from 20-120% predicted, depending on how well the disease is controlled.

The criteria for defining SAFS are:

● Severe asthma (British Thoracic Society step 4 or worse)
● Exclusion of ABPA (total IgE <1000 IU/mL)
● Evidence of sensitisation to one or more fungi, by skin prick test or RAST test

While some patients are sensitised to many fungi, the majority only react to one or two. The most common fungi for patients to be sensitised to are: Aspergillus fumigatus, Penicillium chrysogenum, Cladosporium herbarum, Alternaria alternata, Candida albicans, Trichophyton spp. Skin test results are often not concordant with RAST results. RAST titres (for A. fumigatus) are much lower than titres in patients with ABPA.

Treatment:

Patients with SAFS are usually on multiple medications. Long-term inhaled and frequent courses of oral corticosteroids usually control the patients worst symptoms, but have well known adverse events. These patients are usually already taking either short or long-acting beta-2 agonists, or leukotriene antagonists with some benefit.

Oral itraconazole helps many patients with SAFS by improving asthma control (N.B. therapeutic drug monitoring is advised for itraconazole to optimize exposure — this may require switching between capsules and oral solution, and sometimes raising or lowering the dose). Itraconazole slows the body’s clearance of inhaled steroids in 50% of patients, so steroid side-effects may be magnified. The dose of inhaled steroids should be reduced, if possible. Fluconazole may be beneficial in those sensitised to Trichophyton spp. The required duration of antifungal therapy is uncertain.