Subcutaneous infection of a cat by Colletotrichum species

Subcutaneous infection of a cat by Colletotrichum species

Journal of Feline Medicine and Surgery (2010) 12, 828e830 doi:10.1016/j.jfms.2010.07.005 CASE REPORT Subcutaneous infection of a cat by Colletotrichu...

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Journal of Feline Medicine and Surgery (2010) 12, 828e830 doi:10.1016/j.jfms.2010.07.005

CASE REPORT Subcutaneous infection of a cat by Colletotrichum species Randolph L Winter DVM1*, Sara D Lawhon DVM, PhD, DACVM2, Natalie D Halbert Gwendolyn J Levine DVM2, Heather M Wilson DVM, DACVIM (Oncology)1, Meighan K Daly DVM1 1

Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, USA 2 Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, USA Date accepted: 12 July 2010

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A 13-year-old, domestic shorthair cat was presented for evaluation of a right tarsal mass. Physical examination revealed a 5 cm  5 cm  5 cm, soft, fluctuant, subcutaneous tarsal mass. Thoracic radiographs revealed several discrete lung parenchymal lesions. Abdominal ultrasound revealed abnormal architecture to both kidneys. Fungal culture and sensitivity from the subcutaneous mass revealed a uniform growth of Colletotrichum species that was susceptible to itraconazole. Colletotrichum species infection was confirmed in the subcutis and suspected to be disseminated. Colletotrichum species fungal infections in cats have not been previously documented. Ó 2010 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.

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13-year-old spayed female domestic shorthair cat was presented to the Texas A&M University College of Veterinary Medicine (TAMU-CVM) for evaluation of a subcutaneous mass over the right tarsus. Approximately 2.8 years prior to the patient’s visit to the TAMU-CVM, a mass had been surgically excised at the same location. The histopathologic evaluation of this mass revealed a severe, diffuse, granulomatous dermatitis and cellulitis with intralesional fungi. Fungal identification was not performed, and the organisms were assumed to be non-pathogenic. The cat resides indoors, but has access outdoors. In the 2 months prior to presentation at TAMU-CVM, a mass was observed in the same location. Lameness was noted at home, but the patient was reported to be otherwise healthy. The patient was prescribed enrofloxacin and fluconazole for 3 weeks, which were both discontinued 10 days prior to presentation. On physical examination, an approximately 5 cm  5 cm  5 cm, soft, fluctuant mass was located on the lateral aspect of the right tarsus and involved the subcutis, dermis, and epidermis. The mass had areas of ulceration and erythema. The right popliteal lymph node was mildly enlarged. On thoracic auscultation, a grade II/VI right parasternal systolic *Corresponding author. E-mail: [email protected]

1098-612X/10/100828+03 $36.00/0

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murmur was auscultated. All other physical examination findings were within normal limits. Initial diagnostic evaluation included feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) tests, hematology, serum biochemistry, urinalysis, urine proteinecreatinine ratio, abdominal ultrasound, right tarsal radiographs, thoracic radiographs, and a fine-needle aspirate with cytologic examination of the mass. FeLV and FIV tests were both negative. Hematologic results included an eosinophilia (1648 cells/ml, reference range 0e1500 cells/ml). Significant serum biochemistry results included azotemia (blood urea nitrogen 39 mg/dl, reference range 19e33 mg/dl; creatinine 2.5 mg/dl, reference range 0.8e1.8 mg/dl) and a hyperglobulinemia (4.6 g/dl, reference range 2.3e3.8 g/dl). Urinalysis revealed a urine specific gravity of 1.016 GMS/100 ml, proteinuria (30 mg/dl), and a urine protein:creatinine ratio of 0.41. The findings of the urinalysis and the serum biochemistry revealed the patient was in an International Renal Interest Society (IRIS) stage 2, non-proteinuric, chronic kidney disease.1 Smears prepared from fine-needle aspirates of the mass demonstrated a predominance of macrophages with fewer multinucleated giant cells and mildly degenerate neutrophils admixed with numerous fungal organisms (Fig 1). Fungal organisms were highly pleomorphic in appearance, displaying yeast,

Ó 2010 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.

Subcutaneous infection by Colletotrichum species

Fig 1. Fine-needle aspirate cytology (Diff-Quick stain, 100 objective) from a subcutaneous tarsal swelling in a 13-yearold cat. The hyphal form of a fungal organism (arrow) can be seen with a range in width from 3 to 8 mm, distinct septations, parallel walls, and variably staining granular contents.

pseudohyphal, and hyphal morphology. Macrophages and multinucleated giant cells occasionally contained fungal structures. The cytologic interpretation was pyogranulomatous inflammation with presence of fungal organisms. Right hindlimb radiographs revealed a large softtissue swelling dorsolateral to the distal end of the tibia and fibula. No bone involvement was visualized. Thoracic radiographs revealed several small, ill-defined, soft-tissue density nodules in the lungs. A mild interstitial and bronchial pattern was also identified. Abdominal ultrasound examination revealed that both kidneys had reduced cortical medullary distinction, slightly hypoechoic cortices, and a broad medullary rim sign. Based on the results of the initial diagnostics, tissue samples were collected for fungal culture. Fungal culture from the tarsal mass yielded colonies that were fast-growing and had sparse gray to white aerial mycelium with gray conidia. This fungus was identified as a Colletotrichum species through analysis of 278-bp of the D2 large subunit of the fungal ribosomal DNA (rDNA). The sequence was compared to the MicroSeq (Applied Biosystems) and GenBank databases (query date 28 October 2009). The sequence obtained was 100% homologous with the D2 region of Colletotrichum coccodes, C coffeanum, C gloeosporioides and C caricae. Therefore, the organism is identified here as Colletotrichum species. Antifungal susceptibility testing results at 48 h of growth revealed minimum inhibitory concentrations for fluconazole (>64 mg/ml), itraconazole (0.25 mg/ ml), posaconazole (0.125 mg/ml), and voriconazole (1 mg/ml). Surgical removal of the granuloma and further diagnostics were declined by the owner. Treatment was instituted with oral itraconazole

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(10.8 mg/kg, q 24 h; Patriot Pharmaceuticals), lactated Ringer’s solution fluids to be administered subcutaneously twice a week in the amount of 100 ml, reduced protein diet (k/d, Hill’s), and instructions to keep the patient strictly indoors. Six weeks after the initial examination, the patient had repeated serum biochemistry panel, urinalysis, and thoracic radiographs. Serum biochemistry and urinalysis results revealed a mildly improved hyperglobulinemia, but the patient had progressed to IRIS stage 3, non-proteinuric, chronic kidney disease.1 Thoracic radiographs revealed partial resolution of the pulmonary nodules, as the soft-tissue pulmonary nodules were less distinct as compared to the previous thoracic radiographs. Physical examination of the cat at that time revealed resolution of the ulcerative areas on the tarsal granuloma, but no significant change in size was measurable. The previously reported lameness had resolved. The most common systemic fungal infections in cats include blastomycosis, histoplasmosis, coccidiomycosis, and cryptococcosis, with cryptococcosis representing the most common systemic fungal infection in cats.2,3 Sporothrix species, Mucor species, Candida species, and Penicillium species are also reported to cause systemic fungal disease in cats.3e5 To the authors’ knowledge, Colletotrichum species has not previously been reported in feline patients. Colletotrichum is a fungal pathogen primarily of plants in the humid and subhumid tropics worldwide.6 Colletotrichum species has previously been reported to infect insects, a juvenile Kemp’s Ridley Sea Turtle, and humans.6e12 In the case of the Sea Turtle, a disseminated Colletotrichum species infection developed in the lungs and kidneys secondary to probable immunocompromise from extended hypothermia.8 Reports in humans describe subcutaneous Colletotrichum species infections occurring in patients taking chemotherapy for hematologic malignancies, in a patient self-medicating with prednisone, and ocular infections by Colletotrichum species are described in humans as following some traumatic event such as natural injury or cataract surgery.6,9e12 When presented with subcutaneous masses, fineneedle aspiration with cytologic evaluation can be very useful for identification of the cell type present.13 Differentials for this cat’s subcutaneous mass based on history and physical examination included neoplasia, a bacterial abscess or granuloma, or a fungal infection. Cytologic evaluation of the fine-needle aspirate did not show evidence of neoplasia, an abscess, or a bacterial granuloma as causes of the mass. Fungal organisms that commonly infect cats were not identified in the fine-needle aspirate. As in this cat, when cytologic evaluation does not provide a diagnosis of the specific fungal organism, fungal culture is warranted. Colletotrichum species infection was only verified in the subcutaneous granuloma, not in the kidneys or lungs. Based on improvement of the pulmonary

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lesions with daily itraconazole therapy alone, it is possible that these lesions were fungal in origin, potentially even a dissemination of the Colletotrichum species infection. Considering the overall rarity of subcutaneous and disseminated fungal infections in cats, it is very unlikely that two different fungal infections were present in this patient simultaneously. The patient has no evidence of neoplasia or other cause of pulmonary nodules. It is possible that this cat had chronic kidney disease of non-fungal origin. This would account for the progression of azotemia despite itraconazole therapy. However, it is also possible that fungal nephritis caused the initial damage to the kidneys, and progression of renal disease occurred based on irreversible damage to the nephrons and tubulointerstitial cells. Unfortunately, further diagnostics such as kidney biopsies and bronchoscopy were not performed in this case. It is unclear why this cat developed a Colletotrichum species infection. As Colletotrichum species is almost exclusively plant pathogens and there was a possibility of this being a disseminated disease, the authors believe some degree of immunocompromise may have been present in this animal. Although a FeLV or FIV infection cannot be ruled out without a bone marrow aspirate,14 the absence of any historical or present evidence of illness made retroviral infection a less likely diagnosis. All previous reports of animal infection by Colletotrichum species in extra-ocular locations describe patients with some degree of immune compromise. One paper describes an immunosuppressive peptide, Colutellin A, produced naturally by Colletotrichum dematium.15 In this study, Ren et al found that Colutellin A may possess an immunosuppressive activity even greater than cyclosporin A, a commonly used immunosuppressive in animals. It is unclear what, if any, role this finding played in this cat. In conclusion, this report describes a Colletotrichum species infection verified in the subcutis of a cat and suspected to be a disseminated infection. Fungal culture and susceptibility tests resulted in a correct diagnosis and improvement of clinical signs in this patient.

References 1. Polzin DJ, Osborne CA, Ross S. Chronic kidney disease. In: Ettinger SJ, Feldman EC, eds. Textbook of veterinary internal medicine 6th edn. St Louis: Elsevier Saunders, 2005: 1756e86. 2. Kerl ME. Update on canine and feline fungal diseases. Vet Clin North Am Small Anim Pract 2003; 33: 721e47. 3. Davies C, Troy GC. Deep mycotic infections in cats. J Am Anim Hosp Assoc 1996; 32: 380e91. 4. Dunstan RW, Reimann KA, Langham RF. Feline sporotrichosis. J Am Vet Med Assoc 1986; 189: 880e3. 5. Wray JD, Sparkes AH, Johnson EM. Infection of the subcutis of the nose in a cat caused by Mucor species: successful treatment using posaconazole. J Feline Med Surg 2008; 10: 523e7. 6. Guarro J, Svidzinski TE, Zaror L, Forjaz MH, Gene´ J, Fischman O. Subcutaneous hyalohyphomycosis caused by Colletotrichum gloeosporioides. J Clin Microbiol 1998; 36: 3060e5. 7. Marcelino J, Giordano R, Gouli S, et al. Colletotrichum acutatum var fioriniae (teleomorph: Glomerella acutata var fioriniae var nov) infection of a scale insect. Mycologia 2008; 100: 353e74. 8. Manire CA, Rhinehart HL, Sutton DA, et al. Disseminated mycotic infection caused by Colletotrichum acutatum in a Kemp’s ridley sea turtle (Lepidochelys kempi). J Clin Microbiol 2002; 40: 4273e80. 9. O’Quinn RP, Hoffmann JL, Boyd AS. Colletotrichum species as emerging opportunistic fungal pathogens: a report of 3 cases of phaeohyphomycosis and review. J Am Acad Dermatol 2000; 45: 56e61. 10. Chakrabath A, Shivaprakash MR, Singh R, et al. Fungal endophthalmitis: fourteen years’ experience from a center in India. Retina 2008; 28: 1400e7. 11. Mendiratta DK, Thamke D, Shukla AK, Narang P. Keratitis due to Colletotrichum dematium e a case report. Indian J Med Microbiol 2005; 23: 56e8. 12. Midha NK, Mirzanejad Z, Soni M. Colletotrichum sp: plant or human pathogen? Antimicrob Infect Dis Newsl 1996; 15: 26e7. 13. Carlotti DN. Cutaneous and subcutaneous lumps, bumps, and masses. In: Ettinger SJ, Feldman EC, eds. Textbook of veterinary internal medicine 6th edn. Philadelphia: Elsevier Saunders, 2005: 43e6. 14. August J. Consultations in feline internal medicine. 6th edn. Philadelphia: Saunders, 2009. 15. Ren Y, Strobel GA, Graff JC, Jutila M, Park SG, Gosh S. Colutellin A, an inmmunosuppressive peptide from Colletotrichum dematium. Microbiol 2008; 154: 1973e9.

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