Many gene variants (e.g. CARD9, IL-17) have been described in the literature that predispose patients to fungal infections, but clinical implementation of these results lags behind as many settings currently lack the facilities or funds to carry out genetic investigations.
For detailed reviews see: Lionakis et al, 2014;
Genetic testing for patients with chronic or recurrent fungal infections
Genotyping of patients with fungal infections to detect underlying genetic factors is not currently routine.
Case reports:
- Shi et al (2019) Cutaneous fusariosis caused by Fusarium lichenicola in a child with hyper‐immunoglobulin E syndrome
- A 4yo girl presented with an itchy mass on her face, which tested positive for fungal hyphae and Fusarium DNA (TEF‐1α)
- Whole exome sequencing revealed a STAT3 variant associated with hyper-IgE syndrome (AD-HIES; formerly Job syndrome)
Antifungal prophylaxis for patients with primary immunodeficiencies
General precautions for immunocompromised patients includes avoiding sources of spores (compost, firewood, garden waste, rotting leaves, bird/bat droppings) and the annual flu vaccine.
- Congenital neutropaenia:
- Chronic granulomatous disease:
- Caused by mutations in any subunit of the NADPH oxidase complex (CYBB, CYBA, NCF-1, NCF-2, NCF-4)
- Predisposes to Aspergillus infections
- Prophylaxis with a triazole (often 5 mg/kg daily itraconazole) is recommended (Slack & Thomsen, 2018)
- Test liver enzymes before commencing prophylaxis, and every 6 months thereafter
- See the CGD Society website for more information
Genotyping of CYP variants for TDM
Patients will metabolise azole antifungals at different rates depending on which variants of genes such as CYP2C19, which will affect the dose required. Current practice is to carry out TDM when prescribing voriconazole and itraconazole – for further information please see our TDM webinar.
One trial (VORIGENPHARM) is underway in Spain to test whether pre-emptive genotyping of CYP2C19 is beneficial for patients at high risk of invasive aspergillosis.
Ordering genetic tests
In the UK, consult the National Genomic Test Directory or contact your regional genetics service.