Treatment and Prognosis
Due to lack of prospective treatment trials, evidence-based treatment protocols are not currently available for SNA. Prognosis appears favourable based on the small numbers of cases for which treatment outcomes have been reported.
Signs resolved in 11 of 15 treated cases with follow-up available (Goodall et al. 1984; Tomsa et al. 2003; Whitney et al. 2005; Furrow and Groman 2009; Barrs et al. 2012; Kano et al. 2015). Successful treatment regimens included systemic antifungal therapy in five cases (itraconazole or posaconazole monotherapy or combined with amphotericin B), systemic triazole therapy (itraconazole or posaconazole) combined with topical intranasal clotrimazole or enilconazole infusion in two cases and topical intranasal clotrimazole infusion alone in two cases. Similar to canine SNA (Zonderland et al. 2002), debridement of fungal lesions in the nasal cavity was an integral component of therapy for most cases of feline SNA (Barrs et al. 2012; Tomsa et al. 2003; Goodall et al. 1984; Furrow and Groman 2009). In humans with non-invasive fungal rhinosinusitis due to A. fumigatus infection, sinus fungal plaques can be extensive and form tangled masses of hyphae termed “fungal balls” (Montone et al. 2012). Aggressive endosurgical debridement is usually curative and post-operative or perioperative antifungal treatment is not warranted. In contrast to SNA of dogs and cats, sinonasal fungal balls in humans are not usually associated with nasal bone lysis on CT. However, other similarities of this disease between humans and animals highlight the importance of endoscopic debridement of all visible fungal elements in the therapeutic approach to non-invasive fungal rhinosinusitis (Dufour et al. 2006). A therapeutic strategy for feline SNA, based on previous reports, treatment of canine SNA and consideration of whether infection is invasive or non-invasive, is presented in Table 15.2. Techniques for intranasal clotrimazole infusion in cats are similar to those used for treatment of canine SNA with slight modifications (Furrow and Groman 2009; Tomsa et al. 2003; Peeters and Clercx 2007). Polypropylene glycol must not be used as the vehicle for clotrimazole as it can cause severe mucosal oedema and ulceration (Barr et al. 2010). Polyethylene glycol is a safe vehicle for clotrimazole infusion. As for canine SNA, it may be necessary to repeat endoscopic fungal plaque debridement and intranasal clotrimazole infusion on one or more occasions to effect a cure, and nasal discharge may persist where turbinate destruction is severe (Barrs et al. 2012).Optimal evidence-based treatment protocols for feline SOA are yet to be identified. Prognosis is poor even with aggressive treatment including orbital exenteration combined with systemic antifungal therapy. In the largest case series of 12 cats with SOA for which treatment outcomes could be assessed, all cats were treated with
Table 15.2 Therapeutic approach for treatment of feline sinonasal aspergillosis
• Determine the identity of the fungal isolate and its antifungal susceptibility
• Assess whether infection is invasive or non-invasive based on histopathology and CT findings
• Determine the integrity of the cribriform plate on CT
• Debride all visible fungal plaques/lesions from the nasal cavity and frontal sinuses using endoscopic techniques and saline irrigation
• For non-invasive infections instil an intranasal infusion of 1% clotrimazole in polyethylene glycol (1 h soak under general anaesthesia)
• For invasive infections and/or where A. felis is identified, give additional systemic antifungal therapy (see SOA treatment)
systemic triazole therapy, and five also had orbital exenteration. Treatment was successful in only one case, which did not have exenteration. Relapse of infection occurred 19 months after treatment was stopped, and infection eventually resolved after treatment with caspofungin and posaconazole (Barrs et al.
2012). Of six other cases that responded to systemic antifungal therapy, three of these also had surgical debridement of orbital granulomas, and orbital tissues of one were lavaged at surgery with 1% voriconazole (Smith and Hoffman 2010; Hamilton et al. 2000; McLellan et al. 2006). In only one of these cases was resolution of infection confirmed by follow-up CT (McLellan et al. 2006), and another cat was euthanased 4 months after exenteration with likely progressive disease (Hamilton et al. 2000). Most cats with SOA that responded to systemic antifungal therapy were treated with posaconazole or itraconazole monotherapy or combined with terbinafine and/or amphotericin B for treatment intervals of 6 months or more (Barrs et al. 2012; Kano et al. 2013; McLellan et al. 2006; Hamilton et al. 2000). The importance of antifungal susceptibility testing in guiding therapy is illustrated by one case that failed sequential treatment with itraconazole and amphotericin B but was cured with posaconazole. The section Fumigati isolate from this cat, which was not identified molecularly, had high MICs of amphotericin and itraconazole and a low MIC of posaconazole (McLellan et al. 2006). High MICs of itraconazole and cross-resistance with voriconazole are not uncommon among A. felis and other cryptic species isolates that cause feline URTA. A recent investigation, in which the results of a reference broth microdilution antifungal susceptibility testing method (EUCAST) and a commonly used commercial broth microdilution method (Sensititre YeastOne, Trek Diagnostic System Ltd., East Grinstead, UK) were compared for 90 environmental and clinical isolates from the Aspergillus viridinutans complex, showed that MICs of itraconazole and voriconazole were high. Also, there was poor correlation between the two methods for itraconazole, with the commercial method frequently failing to detect high MICs of itraconazole (Lysokva et al. 2017). A. felis is usually susceptible to amphotericin B (Barrs et al. 2013). Posaconazole is well tolerated after oral administration, and MICs for A. felis are usually lower than voriconazole MICs (Barrs et al. 2013; Lysokva et al. 2017). Voriconazole administration has been associated with severe adverse effects in cats including paraplegia, blindness and anorexia (Quimby et al. 2010; Smith and Hoffman 2010; Barrs et al. 2012). In cats voriconazole has a long oral half-life (>43 h) and non-linear pharmacokinetics are suspected to be the cause of toxicosis at higher drug doses due to saturation of metabolising enzymes and decreased drug clearance (Vishkautsan et al. 2016). Caspofungin was well tolerated and efficacious in one cat with SOA that failed treatment with AMB and posaconazole (Barrs et al. 2012) although in another case treatment with micafungin was unsuccessful (Kano et al. 2008).Serum GM is used to monitor fungal antigen load in humans with aspergillosis, and although it is only elevated in around 30% of cats with SOA, in cats that test positive, this application could be useful to help determine the therapeutic endpoint.
15.9