- Email: [email protected]
Fungal rhinosinusitis caused by Scedosporium apiospermum in a cat
Journal of Feline Medicine and Surgery (2010) 12, 967e971 doi:10.1016/j.jfms.2010.07.004
CASE REPORT Fungal rhinosinusitis caused by Scedosporium apiospermum in a cat Dimitri Leperlier DVM1*, Rosario Vallefuoco DVM1, Eve Laloy DVM, MSc2, Julien Debeaupuits DVM3, Pauline De Fornel Thibaud DVM4, Franc¸ois-Lucien Crespeau DVM, Dipl ECVP2, Jacques Guillot DVM, PhD5 1
Unite´ de Chirurgie, Ecole Nationale Ve´te´rinaire d’Alfort, 7 avenue du Ge´ne´ral De Gaulle, 94700 Maisons-Alfort, France 2 Unite´ d’Anatomie Pathologique, Ecole Nationale Ve´te´rinaire d’Alfort, 7 avenue du Ge´ne´ral De Gaulle, 94700 Maisons-Alfort, France 3 Unite´ de Me´decine, Ecole Nationale Ve´te´rinaire d’Alfort, 7 avenue du Ge´ne´ral De Gaulle, 94700 Maisons-Alfort, France 4 Centre Cance´rologie Ve´te´rinaire d’Alfort, 7 avenue du Ge´ne´ral De Gaulle, 94700 Maisons-Alfort, France 5 Unite´ de Parasitologie, Ecole Nationale Ve´te´rinaire d’Alfort, 7 avenue du Ge´ne´ral De Gaulle, 94700 Maisons-Alfort, France Date accepted: 6 July 2010
A 3-year-old neutered male Bengal cat with a history of chronic mucopurulent bilateral nasal discharge and sneezing was diagnosed with severe fungal rhinosinusitis. A diagnosis was obtained after computer tomography imaging, histopathological examination and fungal culture. The mold Scedosporium apiospermum was identified as the aetiological agent. To our knowledge, this case is the first description of a rhinitis or sinusitis caused by this agent in a cat. Aggressive surgical debridement combined with topical and systemic antifungal therapy was performed. Unfortunately, the treatment resulted only in a partial remission of signs.
Ó 2010 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.
A
3-year-old, household, neutered male Bengal cat was presented to the National Veterinary School of Alfort (France) with a 2.5-year history of mucopurulent bilateral nasal discharge and chronic sneezing. Several antibiotic treatments had been given by the referring veterinarian without improvement. The vaccination status was up to date and feline leukaemia virus (FeLV) and feline immunodeficiency virus (FIV) tests were negative. Neither viral upper respiratory tract infections nor any history of trauma was reported before the onset of clinical signs. On physical examination, the cat was mildly depressed with a rectal temperature of 39.6 C. There was a bilateral mucopurulent nasal discharge
*Corresponding author. E-mail: [email protected]
1098-612X/10/120967+05 $36.00/0
associated with a facial asymmetry due to an apparent firm deformation of the right nasal cavity. Otoscopic and ophthalmological examinations were normal. The remainder of the clinical examination was unremarkable. Differential diagnosis included nasal cavity tumour, foreign body, nasopharyngeal polyp, fungal rhinosinusitis, and idiopathic chronic lymphoplasmacytic rhinitis. Thoracic radiographs were taken to rule out invasive pulmonary diseases and they were normal. Helical computed tomography of the nasal cavity (2 mm thick transverse slices) was then performed revealing a patchy soft tissue/fluid opacification of the right nasal cavity with focal lysis of the nasal turbinates and a homogenous opacification of the entire right frontal sinus with hyperostosis of the frontal bone. These
Ó 2010 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.
968
D Leperlier et al
Fig 1. Transverse computed tomographic (CT) images (window width: 2040, window level: 300) of the nasal cavity. Soft tissue/fluid opacification (30 UH) of the right nasal cavity and frontal sinus (1, 2, 3). Focal lysis of the right nasal turbinates is also present (1, 2). Hyperostosis and thickening of the right frontal bone are seen on images 2 and 3.
images were compatible with a chronic severe inflammatory lesion. There were no signs of a foreign body or nasopharyngeal polyp (Fig 1). Nasal flush samples were submitted for bacteriological culture and cytological evaluation. Cultures were negative and the cytological examination revealed numerous degenerate neutrophils (95% of the cells) and macrophages, without identifiable pathogens. Given the inconclusive nature of the nasal flush, a surgical exploration to retrieve high-quality samples for histopathological examination was planned. A dorsal rhinotomy and sinusotomy with preservation of the bone flap were performed under general anaesthesia. Macroscopically, the greenish material covering the nasosinusal surface was suggestive of
a fungal plaque. Biopsies were obtained before invasive debridement and lavage of the right nasal cavity and sinus. Biopsy material for histological analysis was processed routinely. The epithelium of turbinates and sinus showed foci of erosion and ulceration. The lamina propria was severely infiltrated by neutrophils, lymphocytes, plasma cells, and activated macrophages. It was expanded by a granulation tissue interspersed with haemorrhagic areas. The lymphoid follicles of the nasal-associated lymphoid tissue were hyperplastic. Turbinate bones showed features of osteolysis and osteoproliferation (Fig 2). The fungal plaque was a superficial aggregate of numerous non-pigmented, 3 mm in diameter, evenly septated hyphae with
Fig 2. Chronic-active rhinosinusitis. A. Turbinate: lymphoid follicles with prominent germinative centres are developed from the nasal-associated lymphoid tissue: follicular hyperplasia of the NALT (N); bone is multi-focally disrupted: osteolysis (arrows) or displays osteoproliferation (O). B. Turbinate mucosa: the epithelium is eroded (arrow); the lamina propria is infiltrated by neutrophils, lymphocytes and plasma cells. C. Lamina propria of ulcerated sinus is expanded by a granulation tissue rich in neutrophils, activated macrophages, plasma cells and lymphocytes; there is multifocal haemorrhage without evidence of vasculitis. Haematoxylineeosinesaffron.
Fungal rhinosinusitis by S apiospermum in a cat
969
Fig 3. Fungal plaque containing numerous non-pigmented, 3 mm diameter, evenly septate hyphae and 5e7 mm diameter oval to piriform elements. The plaque is surrounded by degenerate neutrophils, erythrocytes, sloughed epithelial cells, and cell debris. HaematoxylineeosineSaffron. Inset, upper right corner: fungal plaque: the piriform elements may represent asexual spores (conidia) (arrowhead). Haematoxylineeosinesaffron. Inset, lower left corner: Fungal plaque. Grocott methenamine-silver stain.
dichotomous branching at acute angles, interspersed with 5e7 mm diameter oval to piriform elements (Fig 3). Periodic acid-Schiff and Grocott methenamine-silver stainings evidenced hyphae and ovoid elements in the superficial plaque (Fig 3), but not within the nasal tissues. The histological diagnosis was rhinosinusitis, pyogranulomatous, chronic-active, diffuse, severe, focally ulcerative, with obvious fungal plaques. The fungal culture was performed by implanting biopsy tissue fragments on Sabouraud dextrose agar supplemented with chloramphenicol. The colonies displayed annellidic conidiogenesis with solitary conidia. Scedosporium apiospermum, the asexual form of Pseudallescheria boydii, was identified. Minimal inhibitory concentrations were determined using a broth microdilution method derived from the NCCLS (National Committee for Clinical Laboratory Standards, USA) standard for itraconazole, fluorocytosine and terbinafine. The isolate was considered susceptible to itraconazole but resistant to fluorocytosine and terbinafine. Severe chronic rhinosinusitis with multifocal ulceration of the mucosa caused by the fungal species Scedosporium apiospermum was the definitive diagnosis. Sino-nasal irrigation with a 2% enilconazole (Imaveral; Janssen-Cilag) solution was performed. Briefly, the cat was anaesthetised, intubated with a cuffed endotracheal tube and positioned in sternal recumbency. The tip of an 8-French Foley catheter was inserted through the mouth, dorsally to the soft palate and inflated to occlude the nasopharynx, and the pharynx was packed with rolled cotton gauzes. Two 6-French urinary catheters were introduced through both nostrils until the caudal aspect of the nasal cavities. Each sino-nasal cavity was irrigated for 1 h with
125 ml of a warm saline 2% enilconazole solution. Simultaneously, long-term therapy with itraconazole (Sporanox; Janssen-Cilag) at 10 mg/kg (4.5 mg/lb) body weight, PO, q 24 h was initiated. This oral antifungal treatment was continued for 2 months. Partial remission of signs was achieved during these 2 months. The owners declined further treatments several times. The last telephonic follow-up was obtained at 12 months, at which time the cat had clinical signs similar to those of the initial presentation. Scedosporium apiospermum is a ubiquitous filamentous fungus that privileges manure-enriched and polluted environments, and can grow in poorly aerated conditions.1e4 It has been reported as the pathogenic agent of nasal disease in three dogs.5e7 This case is the first description of scedosporiosis in a cat. Several cases of fungal rhinitis have been reported in brachycephalic cats, and although a breed predisposition is suspected, this was not the case here (Bengal breed).8e13 Immune deficiency of human and animal patients is usually mentioned as a predisposing factor to fungal infection. Dogs and cats with localised nasal fungal infection (aspergillosis or cryptococcosis) do not systematically have an immunocompromised condition.8,14,15 In the present case, FIV and FeLV tests were negative and no history of immunodepressive treatments or upper respiratory tract infections was reported. Clinical examination revealed no signs of systemic immunosuppression. It has been suggested that idiopathic chronic lymphoplasmacytic rhinitis could precede and favour a fungal nasal infection in cats.13 In the present case, cytological and histological examinations cannot rule out this possibility. In the reported canine cases of nasal scedosporiosis, histological examination was useful in confirming
970
D Leperlier et al
fungal rhinitis and ruling out inflammatory non-infectious or neoplastic disease.5e7 In superficial mycotic rhinitis in dogs, histological diagnosis required sampling of the fungal plaque.16 The fungus was superficial in two of the reported cases of canine scedosporiosis,6,7 but in one case it invaded deep structures like bone.5 In the present case, the fungal elements remained superficial and an accurate diagnosis may have been missed without sampling of the fungal plaque. Histological examination cannot differentiate S apiospermum and Aspergillus species as the hyphae display a similar morphology in tissues.4,17 The exact identification of the fungal agent is only possible after fungal culture. Culture and sensitivity testing are also crucial for selecting the proper antifungal agents because S apiospermum and Aspergillus species have different sensitivity patterns.17 However, human reports emphasise the importance of cautiously interpreting in vitro antifungal susceptibility results for S apiospermum as they do not always correlate well with in vivo results.4,18 The three reported canine cases of nasal scedosporiosis were all treated with success. In one case,5 S apiospermum was sensitive to ketoconazole, intermediate to clotrimazole, and resistant to itraconazole, fluconazole, amphotericin B and 5-fluorocytosine. The dog was just treated orally with ketoconazole for 30 days with remission of clinical signs. In another case,6 S apiospermum was sensitive to itraconazole, clotrimazole, miconazole, ketoconazole and natamycin, and resistant to terbinafine. The dog had a complete remission of signs without medical treatment. In the third described case,7 empiric oral antifungal treatment with itraconazole was given for 5 weeks without improvement. Then a combined endoscopic curettage associated with a single clotrimazole irrigation was performed with success. In humans, optimal treatment of scedosporiosis is unknown.18 Voriconazole was proposed as a first-line therapy in humans.17,19 Debridement or excision of necrotic tissue and antifungal chemotherapy should be the treatment of choice, but dose and duration have not been established.18 This corresponds to the three-step (surgical debridement, topical and systemic therapy) treatment plan applied to the cat by the authors. In France, in order to prevent inappropriate use, almost all antifungal solutions for irrigation are available only through the hospital pharmacist and are reserved for human use (legal limitations). We, therefore, performed the irrigation with enilconazole, which is available in a liquid presentation for animals. This treatment has resulted in satisfactory outcomes in dogs and cats with severe and recurrent nasal aspergillosis.20 Unfortunately, antifungal sensitivity tests in the present case were performed in a human laboratory and, as a consequence, they did not test enilconazole (a veterinary drug). Even if enilconazole and itraconazole belong to the same family (cross-susceptibility) we could not be certain of the effectiveness
of our irrigation. Therefore, we prescribed an oral treatment of itraconazole given its moderate cost and its legal availability for veterinary use in an oral presentation. In the present case, despite the aggressive surgical debridement and the topical and systemic therapy, the three-step treatment was unsuccessful and there was only a partial remission of signs. We believe that our treatment failure can be explained by the following aspects: (1) the difference between in vitro and in vivo antifungal susceptibility to itraconazole, (2) the unknown effectiveness of the enilconazole infusion, (3) the chronic evolution and extensive aspect of the infection, and (4) a possible underlying idiopathic chronic lymphoplasmacytic rhinitis. Scedosporium apiospermum infection should now be considered in the differential diagnosis for chronic nasal discharge in cats. Diagnosis of fungal infection should be obtained with histopathological evaluation. Fungal culture is necessary for an exact identification of the aetiological agent. Antifungal in vitro susceptibility tests are recommended, but they must be interpreted with caution. There is no standardised therapy for S apiospermum and the treatment remains challenging.
References 1. De Hoog GS, Marvin-Sikkema FD, Lahpoor GA, Gottschall JC, Prins RA, Gue´ho E. Ecology and physiology of the emerging opportunistic fungi Pseudallescheria boydii and Scedosporium prolificans. Mycoses 1994; 37: 71e8. 2. Summerbell RC, Krajden S, Kane J. Potted plants in hospitals as reservoirs of pathogenic fungi. Mycopathologia 1989; 106: 13e22. 3. Hugnet C, Marrou B, Dally C, Guillot J. Osteomyelitis and discospondylitis due to Scedosporium apiospermum in a dog. J Vet Diagn Invest 2009; 21: 120e3. 4. Guarro J, Kantarcioglu AS, Horre R, et al. Scedosporium apiospermum: changing clinical spectrum of a therapyrefractory opportunist. Med Mycol 2006; 44: 295e327. 5. Cabanes FJ, Roura X, Garcia F, Domingo M, Abarca ML, Pastor J. Nasal granuloma caused by Scedosporium apiospermum in a dog. J Clin Microbiol 1998; 36: 2755e8. 6. Coleman MG, Robson MC. Nasal infection with Scedosporium apiospermum in a dog. N Z Vet J 2005; 53: 81e3. 7. Caro-Vadillo A, Garcia-Real I, Paya-Vicens MJ, Sainz-Rodriguez A, Rodriguez-Franco F, Rodriguez-Bertos A. Fungal rhinitis caused by Scedosporium apiospermum in a Labrador Retriever. Vet Rec 2005; 157: 175e7. 8. Goodall SA, Lane JG, Warnock DW. The diagnosis and treatment of a case of nasal aspergillosis in a cat. J Small Anim Pract 1984; 25: 627e33. 9. Hamilton HL, Whitley RD, McLaughlin SA. Exophthalmos secondary to aspergillosis in a cat. J Am Anim Hosp Assoc 2000; 36: 343e7. 10. Tomsa K, Glaus TM, Zimmer C, Greene CE. Fungal rhinitis and sinusitis in three cats. J Am Vet Med Assoc 2003; 222: 1380e4, 1365. 11. Whitney BL, Broussard J, Stefanacci JD. Four cats with fungal rhinitis. J Feline Med Surg 2005; 7: 53e8.
Fungal rhinosinusitis by S apiospermum in a cat
12. Wilkinson GT, Sutton RH, Grono LR. Aspergillus spp infection associated with orbital cellulitis and sinusitis in a cat. J Small Anim Pract 1982; 23: 127e31. 13. Barachetti L, Mortellaro CM, Di Giancamillo M, et al. Bilateral orbital and nasal aspergillosis in a cat. Vet Ophthalmol 2009; 12: 176e82. 14. Sharp NJH. Feline nasal aspergillosisepenicilliosis. Oxford: WB Saunders, 1998: 409. 15. Peeters D, Clercx C. Update on canine sinonasal aspergillosis. Vet Clin North Am Small Anim Pract 2007; 37: 901e6, vi. 16. Caswell JL, Williams JK. Respiratory system. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s pathology of domestic animals. 5th edn. Edinburgh: Elsevier, 2007: 640e1. 17. Schaenman JM, Digiulio DB, Mirels LF, et al. Scedosporium apiospermum soft tissue infection successfully
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treated with voriconazole: potential pitfalls in the transition from intravenous to oral therapy. J Clin Microbiol 2005; 43: 973e7. 18. Cuenca Estrella M, Ruiz Diez B, Martinez Suarez JV, Monzon A, Rodriguez-Tudela JL. Comparative in vitro activity of voriconazole (UK-109,496) and six other antifungal agents against clinical isolates of Scedosporium prolificans and Scedosporium apiospermum. J Antimicrob Chemother 1999; 43: 149e51. 19. Vasoo S, Yeo SB, Lima PL, Anga BS, Lye DC. Efficacy of voriconazole for Scedosporium apiospermum skull base osteomyelitis: case report and literature review. Int J Antimicrob Agents 2008; 31: 184e5. 20. Claeys S, Lefebvre JB, Schuller S, Hamaide A, Clercx C. Surgical treatment of canine nasal aspergillosis by rhinotomy combined with enilconazole infusion and oral itraconazole. J Small Anim Pract 2006; 47: 320e4.
Available online at www.sciencedirect.com
CASE REPORT Fungal rhinosinusitis caused by Scedosporium apiospermum in a cat Dimitri Leperlier DVM1*, Rosario Vallefuoco DVM1, Eve Laloy DVM, MSc2, Julien Debeaupuits DVM3, Pauline De Fornel Thibaud DVM4, Franc¸ois-Lucien Crespeau DVM, Dipl ECVP2, Jacques Guillot DVM, PhD5 1
Unite´ de Chirurgie, Ecole Nationale Ve´te´rinaire d’Alfort, 7 avenue du Ge´ne´ral De Gaulle, 94700 Maisons-Alfort, France 2 Unite´ d’Anatomie Pathologique, Ecole Nationale Ve´te´rinaire d’Alfort, 7 avenue du Ge´ne´ral De Gaulle, 94700 Maisons-Alfort, France 3 Unite´ de Me´decine, Ecole Nationale Ve´te´rinaire d’Alfort, 7 avenue du Ge´ne´ral De Gaulle, 94700 Maisons-Alfort, France 4 Centre Cance´rologie Ve´te´rinaire d’Alfort, 7 avenue du Ge´ne´ral De Gaulle, 94700 Maisons-Alfort, France 5 Unite´ de Parasitologie, Ecole Nationale Ve´te´rinaire d’Alfort, 7 avenue du Ge´ne´ral De Gaulle, 94700 Maisons-Alfort, France Date accepted: 6 July 2010
A 3-year-old neutered male Bengal cat with a history of chronic mucopurulent bilateral nasal discharge and sneezing was diagnosed with severe fungal rhinosinusitis. A diagnosis was obtained after computer tomography imaging, histopathological examination and fungal culture. The mold Scedosporium apiospermum was identified as the aetiological agent. To our knowledge, this case is the first description of a rhinitis or sinusitis caused by this agent in a cat. Aggressive surgical debridement combined with topical and systemic antifungal therapy was performed. Unfortunately, the treatment resulted only in a partial remission of signs.
Ó 2010 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.
A
3-year-old, household, neutered male Bengal cat was presented to the National Veterinary School of Alfort (France) with a 2.5-year history of mucopurulent bilateral nasal discharge and chronic sneezing. Several antibiotic treatments had been given by the referring veterinarian without improvement. The vaccination status was up to date and feline leukaemia virus (FeLV) and feline immunodeficiency virus (FIV) tests were negative. Neither viral upper respiratory tract infections nor any history of trauma was reported before the onset of clinical signs. On physical examination, the cat was mildly depressed with a rectal temperature of 39.6 C. There was a bilateral mucopurulent nasal discharge
*Corresponding author. E-mail: [email protected]
1098-612X/10/120967+05 $36.00/0
associated with a facial asymmetry due to an apparent firm deformation of the right nasal cavity. Otoscopic and ophthalmological examinations were normal. The remainder of the clinical examination was unremarkable. Differential diagnosis included nasal cavity tumour, foreign body, nasopharyngeal polyp, fungal rhinosinusitis, and idiopathic chronic lymphoplasmacytic rhinitis. Thoracic radiographs were taken to rule out invasive pulmonary diseases and they were normal. Helical computed tomography of the nasal cavity (2 mm thick transverse slices) was then performed revealing a patchy soft tissue/fluid opacification of the right nasal cavity with focal lysis of the nasal turbinates and a homogenous opacification of the entire right frontal sinus with hyperostosis of the frontal bone. These
Ó 2010 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.
968
D Leperlier et al
Fig 1. Transverse computed tomographic (CT) images (window width: 2040, window level: 300) of the nasal cavity. Soft tissue/fluid opacification (30 UH) of the right nasal cavity and frontal sinus (1, 2, 3). Focal lysis of the right nasal turbinates is also present (1, 2). Hyperostosis and thickening of the right frontal bone are seen on images 2 and 3.
images were compatible with a chronic severe inflammatory lesion. There were no signs of a foreign body or nasopharyngeal polyp (Fig 1). Nasal flush samples were submitted for bacteriological culture and cytological evaluation. Cultures were negative and the cytological examination revealed numerous degenerate neutrophils (95% of the cells) and macrophages, without identifiable pathogens. Given the inconclusive nature of the nasal flush, a surgical exploration to retrieve high-quality samples for histopathological examination was planned. A dorsal rhinotomy and sinusotomy with preservation of the bone flap were performed under general anaesthesia. Macroscopically, the greenish material covering the nasosinusal surface was suggestive of
a fungal plaque. Biopsies were obtained before invasive debridement and lavage of the right nasal cavity and sinus. Biopsy material for histological analysis was processed routinely. The epithelium of turbinates and sinus showed foci of erosion and ulceration. The lamina propria was severely infiltrated by neutrophils, lymphocytes, plasma cells, and activated macrophages. It was expanded by a granulation tissue interspersed with haemorrhagic areas. The lymphoid follicles of the nasal-associated lymphoid tissue were hyperplastic. Turbinate bones showed features of osteolysis and osteoproliferation (Fig 2). The fungal plaque was a superficial aggregate of numerous non-pigmented, 3 mm in diameter, evenly septated hyphae with
Fig 2. Chronic-active rhinosinusitis. A. Turbinate: lymphoid follicles with prominent germinative centres are developed from the nasal-associated lymphoid tissue: follicular hyperplasia of the NALT (N); bone is multi-focally disrupted: osteolysis (arrows) or displays osteoproliferation (O). B. Turbinate mucosa: the epithelium is eroded (arrow); the lamina propria is infiltrated by neutrophils, lymphocytes and plasma cells. C. Lamina propria of ulcerated sinus is expanded by a granulation tissue rich in neutrophils, activated macrophages, plasma cells and lymphocytes; there is multifocal haemorrhage without evidence of vasculitis. Haematoxylineeosinesaffron.
Fungal rhinosinusitis by S apiospermum in a cat
969
Fig 3. Fungal plaque containing numerous non-pigmented, 3 mm diameter, evenly septate hyphae and 5e7 mm diameter oval to piriform elements. The plaque is surrounded by degenerate neutrophils, erythrocytes, sloughed epithelial cells, and cell debris. HaematoxylineeosineSaffron. Inset, upper right corner: fungal plaque: the piriform elements may represent asexual spores (conidia) (arrowhead). Haematoxylineeosinesaffron. Inset, lower left corner: Fungal plaque. Grocott methenamine-silver stain.
dichotomous branching at acute angles, interspersed with 5e7 mm diameter oval to piriform elements (Fig 3). Periodic acid-Schiff and Grocott methenamine-silver stainings evidenced hyphae and ovoid elements in the superficial plaque (Fig 3), but not within the nasal tissues. The histological diagnosis was rhinosinusitis, pyogranulomatous, chronic-active, diffuse, severe, focally ulcerative, with obvious fungal plaques. The fungal culture was performed by implanting biopsy tissue fragments on Sabouraud dextrose agar supplemented with chloramphenicol. The colonies displayed annellidic conidiogenesis with solitary conidia. Scedosporium apiospermum, the asexual form of Pseudallescheria boydii, was identified. Minimal inhibitory concentrations were determined using a broth microdilution method derived from the NCCLS (National Committee for Clinical Laboratory Standards, USA) standard for itraconazole, fluorocytosine and terbinafine. The isolate was considered susceptible to itraconazole but resistant to fluorocytosine and terbinafine. Severe chronic rhinosinusitis with multifocal ulceration of the mucosa caused by the fungal species Scedosporium apiospermum was the definitive diagnosis. Sino-nasal irrigation with a 2% enilconazole (Imaveral; Janssen-Cilag) solution was performed. Briefly, the cat was anaesthetised, intubated with a cuffed endotracheal tube and positioned in sternal recumbency. The tip of an 8-French Foley catheter was inserted through the mouth, dorsally to the soft palate and inflated to occlude the nasopharynx, and the pharynx was packed with rolled cotton gauzes. Two 6-French urinary catheters were introduced through both nostrils until the caudal aspect of the nasal cavities. Each sino-nasal cavity was irrigated for 1 h with
125 ml of a warm saline 2% enilconazole solution. Simultaneously, long-term therapy with itraconazole (Sporanox; Janssen-Cilag) at 10 mg/kg (4.5 mg/lb) body weight, PO, q 24 h was initiated. This oral antifungal treatment was continued for 2 months. Partial remission of signs was achieved during these 2 months. The owners declined further treatments several times. The last telephonic follow-up was obtained at 12 months, at which time the cat had clinical signs similar to those of the initial presentation. Scedosporium apiospermum is a ubiquitous filamentous fungus that privileges manure-enriched and polluted environments, and can grow in poorly aerated conditions.1e4 It has been reported as the pathogenic agent of nasal disease in three dogs.5e7 This case is the first description of scedosporiosis in a cat. Several cases of fungal rhinitis have been reported in brachycephalic cats, and although a breed predisposition is suspected, this was not the case here (Bengal breed).8e13 Immune deficiency of human and animal patients is usually mentioned as a predisposing factor to fungal infection. Dogs and cats with localised nasal fungal infection (aspergillosis or cryptococcosis) do not systematically have an immunocompromised condition.8,14,15 In the present case, FIV and FeLV tests were negative and no history of immunodepressive treatments or upper respiratory tract infections was reported. Clinical examination revealed no signs of systemic immunosuppression. It has been suggested that idiopathic chronic lymphoplasmacytic rhinitis could precede and favour a fungal nasal infection in cats.13 In the present case, cytological and histological examinations cannot rule out this possibility. In the reported canine cases of nasal scedosporiosis, histological examination was useful in confirming
970
D Leperlier et al
fungal rhinitis and ruling out inflammatory non-infectious or neoplastic disease.5e7 In superficial mycotic rhinitis in dogs, histological diagnosis required sampling of the fungal plaque.16 The fungus was superficial in two of the reported cases of canine scedosporiosis,6,7 but in one case it invaded deep structures like bone.5 In the present case, the fungal elements remained superficial and an accurate diagnosis may have been missed without sampling of the fungal plaque. Histological examination cannot differentiate S apiospermum and Aspergillus species as the hyphae display a similar morphology in tissues.4,17 The exact identification of the fungal agent is only possible after fungal culture. Culture and sensitivity testing are also crucial for selecting the proper antifungal agents because S apiospermum and Aspergillus species have different sensitivity patterns.17 However, human reports emphasise the importance of cautiously interpreting in vitro antifungal susceptibility results for S apiospermum as they do not always correlate well with in vivo results.4,18 The three reported canine cases of nasal scedosporiosis were all treated with success. In one case,5 S apiospermum was sensitive to ketoconazole, intermediate to clotrimazole, and resistant to itraconazole, fluconazole, amphotericin B and 5-fluorocytosine. The dog was just treated orally with ketoconazole for 30 days with remission of clinical signs. In another case,6 S apiospermum was sensitive to itraconazole, clotrimazole, miconazole, ketoconazole and natamycin, and resistant to terbinafine. The dog had a complete remission of signs without medical treatment. In the third described case,7 empiric oral antifungal treatment with itraconazole was given for 5 weeks without improvement. Then a combined endoscopic curettage associated with a single clotrimazole irrigation was performed with success. In humans, optimal treatment of scedosporiosis is unknown.18 Voriconazole was proposed as a first-line therapy in humans.17,19 Debridement or excision of necrotic tissue and antifungal chemotherapy should be the treatment of choice, but dose and duration have not been established.18 This corresponds to the three-step (surgical debridement, topical and systemic therapy) treatment plan applied to the cat by the authors. In France, in order to prevent inappropriate use, almost all antifungal solutions for irrigation are available only through the hospital pharmacist and are reserved for human use (legal limitations). We, therefore, performed the irrigation with enilconazole, which is available in a liquid presentation for animals. This treatment has resulted in satisfactory outcomes in dogs and cats with severe and recurrent nasal aspergillosis.20 Unfortunately, antifungal sensitivity tests in the present case were performed in a human laboratory and, as a consequence, they did not test enilconazole (a veterinary drug). Even if enilconazole and itraconazole belong to the same family (cross-susceptibility) we could not be certain of the effectiveness
of our irrigation. Therefore, we prescribed an oral treatment of itraconazole given its moderate cost and its legal availability for veterinary use in an oral presentation. In the present case, despite the aggressive surgical debridement and the topical and systemic therapy, the three-step treatment was unsuccessful and there was only a partial remission of signs. We believe that our treatment failure can be explained by the following aspects: (1) the difference between in vitro and in vivo antifungal susceptibility to itraconazole, (2) the unknown effectiveness of the enilconazole infusion, (3) the chronic evolution and extensive aspect of the infection, and (4) a possible underlying idiopathic chronic lymphoplasmacytic rhinitis. Scedosporium apiospermum infection should now be considered in the differential diagnosis for chronic nasal discharge in cats. Diagnosis of fungal infection should be obtained with histopathological evaluation. Fungal culture is necessary for an exact identification of the aetiological agent. Antifungal in vitro susceptibility tests are recommended, but they must be interpreted with caution. There is no standardised therapy for S apiospermum and the treatment remains challenging.
References 1. De Hoog GS, Marvin-Sikkema FD, Lahpoor GA, Gottschall JC, Prins RA, Gue´ho E. Ecology and physiology of the emerging opportunistic fungi Pseudallescheria boydii and Scedosporium prolificans. Mycoses 1994; 37: 71e8. 2. Summerbell RC, Krajden S, Kane J. Potted plants in hospitals as reservoirs of pathogenic fungi. Mycopathologia 1989; 106: 13e22. 3. Hugnet C, Marrou B, Dally C, Guillot J. Osteomyelitis and discospondylitis due to Scedosporium apiospermum in a dog. J Vet Diagn Invest 2009; 21: 120e3. 4. Guarro J, Kantarcioglu AS, Horre R, et al. Scedosporium apiospermum: changing clinical spectrum of a therapyrefractory opportunist. Med Mycol 2006; 44: 295e327. 5. Cabanes FJ, Roura X, Garcia F, Domingo M, Abarca ML, Pastor J. Nasal granuloma caused by Scedosporium apiospermum in a dog. J Clin Microbiol 1998; 36: 2755e8. 6. Coleman MG, Robson MC. Nasal infection with Scedosporium apiospermum in a dog. N Z Vet J 2005; 53: 81e3. 7. Caro-Vadillo A, Garcia-Real I, Paya-Vicens MJ, Sainz-Rodriguez A, Rodriguez-Franco F, Rodriguez-Bertos A. Fungal rhinitis caused by Scedosporium apiospermum in a Labrador Retriever. Vet Rec 2005; 157: 175e7. 8. Goodall SA, Lane JG, Warnock DW. The diagnosis and treatment of a case of nasal aspergillosis in a cat. J Small Anim Pract 1984; 25: 627e33. 9. Hamilton HL, Whitley RD, McLaughlin SA. Exophthalmos secondary to aspergillosis in a cat. J Am Anim Hosp Assoc 2000; 36: 343e7. 10. Tomsa K, Glaus TM, Zimmer C, Greene CE. Fungal rhinitis and sinusitis in three cats. J Am Vet Med Assoc 2003; 222: 1380e4, 1365. 11. Whitney BL, Broussard J, Stefanacci JD. Four cats with fungal rhinitis. J Feline Med Surg 2005; 7: 53e8.
Fungal rhinosinusitis by S apiospermum in a cat
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