What is the role of antifungals in allergic fungal disease?

Denning D.W.

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Background: Millions of patients with asthma and allergic fungal sinusitis are sensitized to fungi. Exacerbations of asthma are precipitated by fungal exposure, and asthma severity is also linked to fungal sensitization. Does antifungal therapy help these patients? Published data and clinical experience: There is clear evidence from uncontrolled observations and 2 RCTs that itraconazole is helpful for patients with ABPA. About 60% of patients respond. Some data suggest better response rates at higher itraconazole concentrations. Adverse events rates are moderately high. Relapse is common after discontinuation. Two studies have examined antifungal therapy for severe asthma; on using fluconazole for Trichophyton-sensitized patient, the other for patients sensitized to at least 1 of several fungi (SAFS). Both studies showed marked benefit. With relapse to baseline in the second study, 4 months after discontinuation. In contrast to these positive results, 5 of 6 RCTs for chronic rhinosinusitis were negative rhinitis symptoms improved in the SAFS study with itraconazole, and 12 of 32 (37.5%) refractory patients with allergic fungal rhinosinusitis responded to oral itraconazole over at least 3 months. In my experience, patients who fail or develop toxicity to itraconazole may respond to voriconazole or posaconazole, although data are few. Drug interactions between itraconazole and inhaled steroids are problematic in ~50% patients, increasing steroid exposure. Conclusions: All patients with ABPA and SAFS should be offered oral antifungal therapy. Itraconazole has many drug interactions. Optimisation of exposure with blood level monitoring is preferable. At least 3 months of therapy are required to evaluate response. It is possible itraconazole will be helpful for some patients with chronic fugal rhinosinusitis, but this has yet to be demonstrated in an RCT. Relapse on discontinuation of therapy is usual, but not universal. Azole resistance could supervene, reducing the utility of oral therapy in the future.

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17th International Society for Human and Animal Mycology
    • ISHAM 17th (2009)