A 12-year-old, male, neutered Maine Coon was presented for further investigation of a small nodule on the bridge of his nose. The lesion had recurred following surgical excision eight months previously. Clinical examination was unremarkable except for a well-circumscribed subcutaneous nodule (~2mm diameter) on the bridge of the nose. The lump was non-painful and the overlying skin was intact. Routine haematology and serum biochemistry were unremarkable and ELISA for FIV antibody and FeLV antigen were negative.
fig. 1—histopathology from nasal biopsy showing numerous pink, Periodic Acid Schiff (PAS) stained fungal elements (x20 magnification)
Repeat surgical excision was done and histopathology revealed a granulomatous reaction deep within the dermis. This was interspersed with elongated periodic acid Schiff (PAS) positive bodies and short strands of septate hyphae (fig. 1). Fungal culture yielded a pure growth of Alternaria alternata.
A four-month course of itraconazole (10mg/kg P.O. q24h) was given during which time serum biochemistry was monitored monthly for liver enzyme elevations. The cat remained asymptomatic for eleven months when the nasal swelling recurred. This time the mass was a less well defined, diffuse subcutaneous thickening (fig. 2). It remained non-painful and with no external skin changes or facial deformation. Itraconazole treatment was restarted but over the next two months the lesion remained unchanged and a moderate bilateral mucopurulent nasal discharge developed.
Further diagnostics (blood tests, radiography, rhinoscopy and nasal flushes, Trucut biopsy for histopathology and culture) confirmed recurrence of the fungal granuloma with concurrent bacterial rhinitis but with no evidence of bony or systemic involvement. Following a two week course of amoxicillin clavulanate (75mg P.O. q12h) the nasal discharge resolved. However, despite ‘in vitro’ sensitivity to itraconazole, the fungal mass failed to reduce in size. A third surgical excision was therefore performed, this time with removal of an area of underlying bone. Analgesia with morphine (0.7mg IM) and meloxicam (0.7mg P.O.) were given peri-operatively, itraconazole was continued and adjunctive treatment with terbinafine (250mg P.O. q24h) was started. Haematology and serum biochemistry were monitored weekly for the first four weeks and then monthly. After five months of treatment the terbinafine was stopped. The cat remained asymptomatic for the following five years until he was eventually euthanased due to cardiac failure as a result of hypertrophic cardiomyopathy.
Conclusions and Discussion:
fig. 2—photograph showing a poorly defined, raised, subcutaneous swelling on the bridge of the nose.
Alternaria infection often appears as slow-growing, poorly circumscribed, cutaneous lesions that can be nodular or plaque like in appearance. It should also be considered as a differential diagnosis for non-healing wounds. The extremities, particularly the nose, pinnae and digits appear to be predisposed and, although the majority of lesions are focal, multifocal disease is also possible. Systemic involvement has not yet been identified in cats. Lesions are generally non-painful although secondary ulceration is common, resulting in mild discomfort. Lesions can be locally aggressive and are also unsightly, particularly when on the face. There is potential for spread to other sites and to other animals via cutaneous lesions and there is also a potential zoonotic risk, particularly for immunosuppressed individuals.
Obtaining a definitive diagnosis is essential before embarking on potentially long and invasive treatment strategies. Histopathology is not a reliable tool for speciation and Alternaria may be mistaken for other fungi such as Cryptococcus (Mayser, Nilles et al. 2002). Fungal culture is therefore recommended in order to obtain a definitive diagnosis. This also enables antifungal sensitivity assays to be done, which is a useful tool if disease is recurrent following initial treatment. In the future, molecular identification may have the benefit of a more rapid result but this is not yet widely available (Lo Cascio, Ligozzi et al. 2004).
First line therapy is usually the azoles. Itraconazole or fluconazole are the drugs of choice and, given the high incidence of recurrence, should be continued for at least two months following resolution of clinical signs. Ketoconazole is generally felt to be less effective and has more side effects, so is only advocated when costs are an issue (Moriello 1995). Long courses of medical therapy are required and the side-effects, particularly hepatotoxicity, can be a limiting factor. Alternative treatments include amphotericin B and terbinafine hydrochloride. Terbinafine, a highly lipophilic allylamine antifungal, is a relatively new drug in terms of veterinary use. It is fungicidal and is concentrated in the skin, nails and fat following oral dosing, making it a good choice for dermatological infections, particularly ringworm (Mancianti et al 1999). There has been limited experience of its use in cats, but side effects are thought to be rare. Intravenous liposomal amphotericin B administration is the mainstay of treatment for human systemic fungal infections (Sorensen, Becker et al. 2006). This drug has been rarely used in veterinary medicine because it is prohibitively expensive and in its cheaper desoxycholate form it is highly nephrotoxic. However, reduced nephrotoxicity has been described using subcutaneous administration making it a more practical option (O’Brien, Krockenberger et al. 2006).
Surgical excision or debulking is an important aspect of therapy and should be considered in all cases. Surgery alone can be curative if radical excision is possible. However, lesions appear to be very persistent and recurrence is common despite aggressive treatment. Therefore, a combination of surgical excision and adjunctive medical therapy should be used if surgical margins can not be guaranteed. It appears that disease may be controlled effectively using medical therapy alone but complete cure may not be achieved. Given the potential side effects of long term drug therapy this should only be advocated if the lesions are multifocal or not amenable to surgery.
References:
Lo Cascio, G., M. Ligozzi, et al. (2004). Utility of molecular identification in opportunistic mycotic infections: a case of cutaneous Alternaria infectoria infection in a cardiac transplant recipient. J Clin Microbiol 42(11): 5334-6.
Mayser P, Nilles M, de Hoog G S (2002) Case report. Cutaneous phaeohyphomycosis due to Alternaria alternata. Mycoses 45 338-40
Moriello K A, DeBoer D J (1991) Fungal flora of the coat of pet cats. Am J Vet Res 52 602-6
O’Brien, C. R., M. B. Krockenberger, et al. (2006). Long-term outcome of therapy for 59 cats and 11 dogs with cryptococcosis. Aust Vet J 84(11): 384-92.
Sorensen, J., M. Becker, et al. (2006). Rhinocerebral zygomycosis in a young girl undergoing allergenic stem cell transplantation for severe aplastic anaemia. Mycoses 49 Suppl 1: 31-6.
