History
A 5-year-old 499-kg (1,098-lb) castrated male Quarter Horse was submitted to the Oklahoma State University Animal Disease Diagnostic Laboratory because of a 6-week history of unilateral epistaxis from the right naris. Multiple antimicrobial treatments had been ineffective. Nasal endoscopic examination had revealed proliferative tissue covering the left auditory tube diverticulum (guttural pouch) opening and the surrounding areas. Because of financial constraints, the owner elected euthanasia of the horse.
Clinical and Gross Findings
The horse had a body condition score of 4 of 9. Necropsy revealed that the subcutaneous and visceral adipose tissues were diffusely dark yellow. The right naris was soiled by fresh blood. The right nasal septum was thickened, in an approximately 10 × 6-cm area, by raised, multi-focal to coalescing, irregular ulcerated masses, which were surrounded by light gray friable necrotic tissue and pools of hemorrhagic material (Figure 1). Few similar, isolated, raised ulcerated masses were also present in the larynx, at the opening of the right and left guttural pouches, and in the mucosa of the proximal ventrolateral portion of the trachea. There were no gross lesions in the guttural pouches. Retropharyngeal and cervical lymph nodes were mildly large with thickened cortex and indistinct medulla on cut section.
Photograph of the right nasal cavity of a 5-year-old Quarter Horse that was evaluated because of a 6-week history of unilateral epistaxis from the right naris. Notice that the right nasal septum is thickened by raised, multifocal to coalescing, irregular ulcerated masses (arrows) and areas of hemorrhage, which are surrounded by light gray friable necrotic material and pale, firm fibrotic areas. In this view, the nasal concha and hard palate (black arrowhead) are identified; rostral and caudal orientation of the nasal cavity is also indicated.
Citation: Journal of the American Veterinary Medical Association 236, 8; 10.2460/javma.236.8.831
Photograph of the right nasal cavity of a 5-year-old Quarter Horse that was evaluated because of a 6-week history of unilateral epistaxis from the right naris. Notice that the right nasal septum is thickened by raised, multifocal to coalescing, irregular ulcerated masses (arrows) and areas of hemorrhage, which are surrounded by light gray friable necrotic material and pale, firm fibrotic areas. In this view, the nasal concha and hard palate (black arrowhead) are identified; rostral and caudal orientation of the nasal cavity is also indicated.
Citation: Journal of the American Veterinary Medical Association 236, 8; 10.2460/javma.236.8.831
Photograph of the right nasal cavity of a 5-year-old Quarter Horse that was evaluated because of a 6-week history of unilateral epistaxis from the right naris. Notice that the right nasal septum is thickened by raised, multifocal to coalescing, irregular ulcerated masses (arrows) and areas of hemorrhage, which are surrounded by light gray friable necrotic material and pale, firm fibrotic areas. In this view, the nasal concha and hard palate (black arrowhead) are identified; rostral and caudal orientation of the nasal cavity is also indicated.
Citation: Journal of the American Veterinary Medical Association 236, 8; 10.2460/javma.236.8.831
Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page →
Histopathologic Findings
Initially, the main differential diagnoses for this horse included a granulomatous process and a malignant tumor. Histologic examination of sections of the right naris revealed that the mucosa and submucosa were markedly infiltrated and expanded by numerous granulomas. The granulomas were composed of peripheral aggregates of epithelioid macrophages and multi-nucleated giant cells admixed with variable numbers of intact and degranulated eosinophils, intact and degenerated neutrophils, hemosiderophages, lymphocytes, and plasma cells; the aggregates were surrounded regionally by fibrous connective tissue (Figure 2). The core of these granulomas contained clubs of eosinophilic material admixed with degranulated eosinophilic granules; the clubs were arranged in a palisading pattern (Splendore-Hoeppli phenomenon) and were centered on longitudinal and cross-sectional profiles of short-length, non-pigmented, occasionally branching, and rarely septate fungal hyphae of variable width (approx 4 to 14 μm in diameter; Figure 3). The hyphae were surrounded by thick, non-parallel, irregularly wavy walls (Figure 4). Fibroblasts and endothelial cells had prominent plump nuclei, and submucosal vessels were markedly congested. Regional hyperplasia and squamous metaplasia of overlying ciliated pseudostratified columnar nasal epithelium were also present. The cortex of the cranial cervical lymph node was thickened by numerous secondary reactive follicles that were surrounded by prominent paracortical zones. Results of fungal culture of specimens of nasal mucosa confirmed the identity of the organism as Conidiobolus coronatus.
Photomicrograph of a section of the nasal submucosa of the right naris in the horse in Figure 1. Notice the granuloma that is characterized by a peripheral rim of fibroblasts, lymphocytes, plasma cells, eosinophils, and neutrophils that surrounds epithelioid macrophages (arrowheads) and multinucleate giant cells (arrows). H&E stain; bar = 50 μm.
Citation: Journal of the American Veterinary Medical Association 236, 8; 10.2460/javma.236.8.831
Photomicrograph of a section of the nasal submucosa of the right naris in the horse in Figure 1. Notice the granuloma that is characterized by a peripheral rim of fibroblasts, lymphocytes, plasma cells, eosinophils, and neutrophils that surrounds epithelioid macrophages (arrowheads) and multinucleate giant cells (arrows). H&E stain; bar = 50 μm.
Citation: Journal of the American Veterinary Medical Association 236, 8; 10.2460/javma.236.8.831
Photomicrograph of a section of the nasal submucosa of the right naris in the horse in Figure 1. Notice the granuloma that is characterized by a peripheral rim of fibroblasts, lymphocytes, plasma cells, eosinophils, and neutrophils that surrounds epithelioid macrophages (arrowheads) and multinucleate giant cells (arrows). H&E stain; bar = 50 μm.
Citation: Journal of the American Veterinary Medical Association 236, 8; 10.2460/javma.236.8.831
Photomicrograph of a section of the nasal submucosa of the right naris in the horse in Figure 1. In this area, clubs of eosinophilic material (arrowheads) admixed with degranulated eosinophilic granules are arranged in a palisading pattern (Splendore-Hoeppli phenomenon) and surround hyphae (arrows). Numerous eosinophils and neutrophils are present in the background tissue. H&E stain; bar = 50 μm.
Citation: Journal of the American Veterinary Medical Association 236, 8; 10.2460/javma.236.8.831
Photomicrograph of a section of the nasal submucosa of the right naris in the horse in Figure 1. In this area, clubs of eosinophilic material (arrowheads) admixed with degranulated eosinophilic granules are arranged in a palisading pattern (Splendore-Hoeppli phenomenon) and surround hyphae (arrows). Numerous eosinophils and neutrophils are present in the background tissue. H&E stain; bar = 50 μm.
Citation: Journal of the American Veterinary Medical Association 236, 8; 10.2460/javma.236.8.831
Photomicrograph of a section of the nasal submucosa of the right naris in the horse in Figure 1. In this area, clubs of eosinophilic material (arrowheads) admixed with degranulated eosinophilic granules are arranged in a palisading pattern (Splendore-Hoeppli phenomenon) and surround hyphae (arrows). Numerous eosinophils and neutrophils are present in the background tissue. H&E stain; bar = 50 μm.
Citation: Journal of the American Veterinary Medical Association 236, 8; 10.2460/javma.236.8.831
Photomicrograph of a section of the nasal submucosa of the right naris in the horse in Figure 1. Longitudinal and cross-sectional profiles of nonpigmented, focally branching, fungal hyphae (approx 4 to 14 μm in diameter [arrows]) are surrounded by thick, nonparallel, and irregularly wavy walls. Gomori methenamine silver stain; bar = 50 μm.
Citation: Journal of the American Veterinary Medical Association 236, 8; 10.2460/javma.236.8.831
Photomicrograph of a section of the nasal submucosa of the right naris in the horse in Figure 1. Longitudinal and cross-sectional profiles of nonpigmented, focally branching, fungal hyphae (approx 4 to 14 μm in diameter [arrows]) are surrounded by thick, nonparallel, and irregularly wavy walls. Gomori methenamine silver stain; bar = 50 μm.
Citation: Journal of the American Veterinary Medical Association 236, 8; 10.2460/javma.236.8.831
Photomicrograph of a section of the nasal submucosa of the right naris in the horse in Figure 1. Longitudinal and cross-sectional profiles of nonpigmented, focally branching, fungal hyphae (approx 4 to 14 μm in diameter [arrows]) are surrounded by thick, nonparallel, and irregularly wavy walls. Gomori methenamine silver stain; bar = 50 μm.
Citation: Journal of the American Veterinary Medical Association 236, 8; 10.2460/javma.236.8.831
Morphologic Diagnosis
Severe chronic diffuse pyogranulomatous, necrohemorrhagic, and eosinophilic rhinitis with intralesional fungal hyphae (morphologically consistent with Conidiobolus spp).
Comments
Conidiobolus spp and Basidiobolus spp are saprophytic fungi of the class Zygomycetes and order Entomophthorales. Conidiobolus coronatus is associated with nasal entomophthoromycosis in horses but can also cause lesions on the facial skin and in the retropharyngeal area, retrobulbar space, brain, maxillary sinus, guttural pouches, and trachea.1 Conidiobolus coronatus infections are mostly limited to tropical and subtropical climates. In contrast to members of the order Mucorales (Mucor, Absidia, and Rhizopus spp) that cause zygomycosis in immunocompromised animals, members of the order Entomophthorales affect immunocompetent animals. In the horse of this report, pathological changes suggestive of immunosuppression, including concurrent infection or metabolic diseases, were not evident. Because the lesions were restricted to only the right nasal cavity, an initial traumatic injury was suspected, but no foreign body was observed either grossly or histologically. Infections with Conidiobolus spp, Basidiobolus spp, and Pythium insidiosum are traditionally grouped together as phycomycosis because of similar clinical signs. Moreover, these organisms have similar histologic characteristics and morphology; therefore, fungal culture is required for definitive identification.
Common clinical signs of nasopharyngeal Conidiobolus infection are nonspecific and include serosanguinous mucopurulent nasal discharge and dyspnea and abnormally noisy respiration secondary to the narrowing of nasal and nasopharyngeal passages associated with development of underlying fibrosis and inflammation. The gross lesions in the nostrils and surrounding skin are typically composed of necrotizing, ulcerating, and cavitating granulomas with serosanguineous exudate that contains small, gritty, yellow-white, coral-shaped granules known as kunkers or leeches. Kunkers associated with Conidiobolus and Basidiobolus infections are smaller than those associated with Pythium infections. In addition to the ulcerated mucosa, the nostrils, nasal cavity, and nasopharynx may also contain pedunculated nodules. Histologically, areas of pyogranulomatous, necrotizing, and eosinophilic inflammation with multinucleated giant cells, fibrosis, and Splendore-Hoeppli bodies often surround the hyphae. Splendore-Hoeppli bodies are currently considered a result of precipitation of immune complexes. Conidiobolus coronatus hyphae are nonpigmented, broad (5 to 12.8 μm in width), thin walled, occasionally septate, irregular in contour, and irregularly branched. Although the morphology of Basidiobolus and Pythium organisms and patterns of infection-associated inflammation are nearly identical to those of Conidiobolus spp, the hyphae of Basidiobolus spp are slightly larger (5 to 20 μm in diameter) and Pythium hyphae are more narrow (2 to 7 μm in diameter), thick walled, and infrequently septate. In Pythium-infected animals, lesions are commonly located on the distal portion of the limbs and the ventral aspect of the trunk. In tissue sections, the eosinophilic sleeve surrounding Conidiobolus organisms is thicker than that which surrounds Pythium organisms. In contrast to C coronatus, the hyphae of fungi that cause phaeohyphomycosis are pigmented and Aspergillus hyphae are non-pigmented, septate, and 2 to 6 μm in diameter, with dichotomous branching. Fungal isolation of C coronatus is required for definitive diagnosis because immunohistochemical and serologic analyses are not currently available. Similar inflammatory changes develop in association with habronemiasis and mast cell tumors. However, both of those diseases are easily differentiated histologically from infection with Conidiobolus spp by the presence of nematode larvae and neoplastic mast cells, respectively, and the absence of fungal organisms.
Several treatment protocols for nasopharyngeal conidiobolomycosis in horses have been evaluated, including complete surgical excision, debulking of infected tissue with intralesional injection of amphotericin B,2 intralesional injection of amphotericin B with adjunct sodium iodide or potassium iodide,3 and oral administration of fluconazole.4 Oral treatment with itraconazole alone is considered ineffective.5
References
- 1.↑
Steiger RR, Williams MA. Granulomatous tracheitis caused by Conidiobolus coronatus in a horse. J Vet Intern Med 2000;14:311–314.
- 2.↑
French DD, Haynes PF, Miller RI. Surgical and medical management of rhinophycomycosis (conidiobolomycosis) in a horse. J Am Vet Med Assoc 1985;186:1105–1107.
- 3.↑
Zamos DT, Schumacher J, Loy JK. Nasopharyngeal conidiobolomycosis in a horse. J Am Vet Med Assoc 1996;208:100–101.
- 4.↑
Taintor J, Crowe C, Hancock S, et al. Treatment of conidiobolomycosis with fluconazole in pregnant mares. J Vet Intern Med 2004;18:363–364.
- 5.↑
Korenek NL, Legendre AM, Andrews FM, et al. Treatment of mycotic rhinitis with itraconazole in three horses. J Vet Intern Med 1994;8:224–227.
