A 12-year-old 500-kg (1,100-lb) American Quarter Horse mare was referred to the University of Tennessee's Veterinary Medical Teaching Hospital because of continuous, mucopurulent, bloody, foul-smelling discharge from the left nostril, inspiratory dyspnea, and abnormal respiratory noise that had first been observed 5 months previously. The horse had been treated with various antimicrobial drugs, a corticosteroid, and an antihistamine; despite treatments, clinical signs of respiratory tract disease persisted. Bacterial and fungal culture of nasal exudate had yielded colonies of Cryptococcus neoformans, along with microflora typically found in the nasal cavities. The result of a cryptococcal antigen detection latex agglutination assaya performed prior to referral was negative.
During the initial examination of the horse, severe inspiratory dyspnea and stertorous respiration were detected. A temporary tracheostomy was performed to improve respiration and facilitate further physical examination. During rhinoscopy, a tan mass that protruded from the left middle nasal meatus (at the nasomaxillary drainage angle) into the left common nasal meatus was observed. The mass obstructed most of the left nasal cavity; it extended caudally into the nasopharynx and around the caudal edge of the nasal septum into the right nasal cavity. A specimen of the mass was obtained through the endoscopic biopsy channel. In laterolateral and dorsoventral radiographic views of the horse's skull, a soft tissue opacity was associated with most of the left nasal cavity and left paranasal sinuses (Figure 1). On the basis of radiographic observations, it was concluded that the mass likely originated from tissue within the left paranasal sinuses and extended into the nasal cavity either through the nasomaxillary aperture or through erosion of the conchae. Hematologic abnormalities included mild anemia and hypoalbuminemia. The result of a cryptococcal antigen enzyme immunoassayb performed on a serum sample was negative. Cytologic examination of impression smears of tissue from the nasal mass revealed evidence of pyogranulomatous inflammation and thickly encapsulated, narrow-based budding yeast forms typical of C neoformans (Figure 2). To treat the horse, removal of the mass from the left paranasal sinuses was recommended. On the basis of the cytologic findings, it was assumed that the mass was a result of cryptococcal infection of the left paranasal sinuses.
Lateral radiographic view of the skull of a horse that was evaluated because of continuous, mucopurulent, bloody, foul-smelling discharge from the left nostril, inspiratory dyspnea, and abnormal respiratory noise of 5 months' duration. Notice the soft tissue opacity in the left paranasal sinuses and nasal cavity (white arrows) attributable to a cryptococcal granuloma.
Citation: Journal of the American Veterinary Medical Association 234, 4; 10.2460/javma.234.4.509
Photomicrograph of an impression smear of tissue obtained from the nasal mass in the horse in Figure 1. Notice the thickly encapsulated yeast forms typical of Cryptococcus neoformans (including one with characteristic narrow-based budding) and evidence of pyogranulomatous inflammation. Wright stain; bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 234, 4; 10.2460/javma.234.4.509
The horse was sedated with detomidine (0.02 mg/kg [0.01 mg/lb], IV) and butorphanol (0.01 mg/kg [0.005 mg/lb], IV). The left paranasal sinuses were exposed through creation of a 3-sided, frontonasal, osteoplastic flap. The horse was administered xylazine (0.5 mg/kg [0.23 mg/lb], IV) twice during the procedure. To desensitize the left paranasal sinuses, anesthesia of the left maxillary nerve at the maxillary foramen in the pterygopalatine fossa was achieved via injection of 8 mL of 2% mepivacaine hydrochloride. The surgical site was prepared for surgery, and the proposed site of incision was infused SC with 20 mL of 2% mepivacaine hydrochloride. The surgical site was left undraped to better monitor the horse's reactions to surgical manipulations.
To create the frontonasal flap on the left side of the head, a rectangular, cutaneous incision with rounded corners that extended through the periosteum was made over the conchofrontal sinus. The caudal portion of the incision was made perpendicular to the dorsal midline midway between the supraorbital foramen and the medial canthus of the left eye. This portion of the incision extended laterally from the dorsal midline to 2 cm medial to the medial aspect of the rim of the orbit. The rostral portion of the incision extended laterally from the dorsal midline (from a point approx 2 cm caudal to where the nasal bones began to diverge) to an imaginary line between the medial canthus of the eye and the nasoincisive notch. The lateral portion of the incision connected the lateral extent of the caudal and rostral portions of the incision and was parallel to the dorsal midline. The margins of the periosteal incision were reflected several millimeters by use of a periosteal elevator, and the bone at the depth of the incision was incised by use of an oscillating cast cutting saw.c The bone was incised at a 45° angle so that its external lamina was slightly larger than its internal lamina, and the axial aspect of the flap was fractured and folded axially. A viscous, foul-smelling, homogeneously white, purulent exudate flowed from the sinuses. Exudate within the sinuses was evacuated via lavaging with sterile, physiologic saline (0.9% NaCl) solution; as a result, a large tan mass that completely filled and distorted the sinuses was exposed (Figure 3). The mass was removed from the sinuses via dissection with fingers and sponge tissue forceps. The base of the mass was the ethmoid labyrinth. The mass had distorted normal architecture of the sinuses so that conchae were eroded and the sinuses appeared to be 1 large cavity. The hole in the conchae was enlarged with scissors to expose the caudal half of the left nasal cavity and the rostral portion of the nasopharynx. Surgery was accompanied by moderate hemorrhage that obscured observation of the sinuses.
Photograph obtained during frontonasal sinusotomy in the horse in Figure 1. A tan mass (grasped within the forceps) was present in the left paranasal sinuses.
Citation: Journal of the American Veterinary Medical Association 234, 4; 10.2460/javma.234.4.509
The flap was replaced to its original position; subcutaneous tissue was apposed with 6 widely spaced, simple interrupted, 2-0 polydiaxonone sutures, and the skin incision was closed with staples. To protect and compress the surgical site, the flap was covered with gauze swabs, which were anchored with an elastic, adhesive bandage that encircled the horse's forehead. The horse received phenylbutazone (4.4 mg/kg [2 mg/lb], PO, q 12 h) before surgery and for 3 days (2.2 mg/kg [1 mg/lb], PO, q 12 h) after surgery. The horse was administered trimethoprim-sulfadiazine (20 mg/kg [9.1 mg/lb], PO, q 12 h) for 2 days before surgery and for 4 days after surgery. The horse was treated with fluconazole (5 mg/kg [2.27 mg/lb], PO, q 24 h) for 4 weeks.
Because hemorrhage during surgery had obscured the surgical site, the left paranasal sinuses were reexamined through the frontonasal, osteoplastic flap the day after surgery to determine whether any of the fungal lesion remained. After the horse was sedated, the staples and subcutaneous sutures were removed, the flap was elevated, and a large blood clot was removed to enable examination of the sinuses. Examination revealed that a 5-mm-diameter lesion (similar in appearance to the granulomatous lesion removed the day before) remained attached to the ethmoid labyrinth. This lesion was removed with sponge forceps, and the flap was replaced and secured with sutures and staples in a manner identical to that used to secure the flap the day before. A 24-F Foley catheter was inserted through the frontal bone at the dorsolateral corner of the osteoplastic flap so that the sinuses could be lavaged, and the head was rebandaged. The tracheostomy tube was cleaned daily until it was removed 2 days later. Enilconazoled (50 mL of a 10% solution) was instilled into the paranasal sinuses through the Foley catheter every other day, and the owner was instructed to continue this treatment until 7 lavages were completed. Results of bacterial and fungal cultures and histologic examination of the tissue removed from the left paranasal sinuses confirmed infection with C neoformans. Antimicrobial susceptibility testing revealed that the organisms were susceptible to fluconazole and itraconazole. The horse was discharged from the hospital 4 days after surgery. The owner was instructed to have the Foley catheter and skin staples removed 10 days after the final treatment with enilconazole. The horse was confined to a stall at home for 3 weeks with hand walking. The tracheostomy site was cleaned daily, and the bandage on the head was changed as needed.
On examination of the horse 6 weeks after surgery, clear nasal discharge from the left nasal cavity was evident. During endoscopic examination of the nasal cavities, a large opening in the nasal conchae that allowed observation of the sinusal portion of the ethmoid labyrinth was detected; the site of the fungal mass on the ethmoid labyrinth was smooth and covered with epithelium. No soft tissue opacity was visible in laterolateral and dorsoventral radiographic views of the skull (Figure 4).
Lateral radiographic view of the skull of the horse in Figure 1 obtained 6 weeks after surgery. Notice that the soft tissue opacity detected in the the left paranasal sinuses and nasal cavity is no longer visible.
Citation: Journal of the American Veterinary Medical Association 234, 4; 10.2460/javma.234.4.509
Discussion
Cryptococcosis is a granulomatous fungal disease of domestic animals and humans; it usually affects the skin, meninges and brain, or respiratory system and is caused by the yeast C neoformans.1,2 In horses, the nervous and respiratory systems are most commonly affected, and the most frequently reported site of infection is the nasal cavity and associated paranasal sinuses.3–7 However, the disease in any form in horses is infrequently reported.2,6,7 Cryptococcus neoformans is a ubiquitous saprophyte that is typically found in soil polluted by bird droppings,1,3–5,8 and respiratory tract infection is acquired via inhalation of dust contaminated with the organism.7 Damaged tissue may be predisposed to infection with Cryptococcus organisms, at least in the nasal form of the disease.4,5 Such damage might occur during passage of a nasogastric tube or from other diseases of the nasal cavity or paranasal sinuses, such as bacterial or viral infection or neoplasia.9,10 All immunocompromised domestic animals and humans are predisposed to infection, but transmission from one host to another has not been clearly demonstrated.2,5,8 Virulence factors of this yeast are related to its polysaccharide capsule and mannoproteins7,11 The capsule blocks interaction of bound antibodies with receptors on host phagocytes and thus inhibits phagocytosis.7,12
Clinical signs of sinonasal cryptococcosis in horses include anorexia; fever; unilateral, chronic, malodorous, sanguinolent or mucopurulent nasal discharge; epistaxis; sneezing; dysphagia; stertorous breathing; reduced airflow from 1 or both nasal cavities; dyspnea; and facial deformity.2–7,13 Differential diagnoses include fungal plaques caused by Aspergillus spp and Pseudoallescheria boydii; nasal granuloma caused by periapical infection of a maxillary premolar or by other fungi that infect the nasal mucosa, such as Rhinosporidium seeberii, Basidiobolus haptosporus, Conidiobolus coronatus, and Coccidioides immitis; ethmoidal hematoma; and neoplasia.2,10,13–15
Diagnosis of cryptococcosis is based on clinical signs, cytologic identification of the causative organism, gross and histologic appearance of the lesion, and results of serologic assessments or fungal culture.2,3,16 During endoscopic examination or surgery of the affected nasal cavity or paranasal sinuses, a yellowish or tan gelatinous mass is typically visible. In general, microscopic examination of a sample of nasal exudate stained with periodic acid–Schiff stain or India ink reveals the characteristic, thickly encapsulated, budding yeasts. Histologic examination of a section of a lesion caused by C neoformans usually reveals evidence of an inflammatory response (mixed population of inflammatory cells) and periodic acid–Schiff–positive, thickly encapsulated yeast bodies (5 to 30 Pm in diameter).2,3 Culture of C neoformans requires 3 to 5 days.2 The latex agglutination test has been used to diagnose cryptococcosis in humans and cats,17 and test results have been reported as helpful in the diagnosis of cryptococcal pneumonia in a pony.6
Historically, treatment of horses with a nasal granuloma caused by C neoformans has been unsuccessful.2–4,6,7,12,18–20 Treatment has included excision of the granuloma, cryotherapy, and parenteral administration of sodium iodide, antimicrobials, and antifungal drugs, especially amphotericin B. Oral administration of fluconazole has been effective in dogs and cats to treat systemic fungal infections such as cryptococcosis17,18,20 and in horses for other local and systemic fungal diseases.21,22 Topical infusion of 0.2% enilconazole combined with oral administration of antifungals has been useful in the treatment of dogs and cats with sinonasal aspergillosis and horses with mycosis of the auditory tube diverticula23–26; enilconazole appears to be less irritating and toxic than other topically applied antifungal agents.24–26
In the horse of this report, the frontonasal flap was opened the day after surgery to allow direct examination of the paranasal sinuses for remnants of the mass without hemorrhage obscuring the view. Because a large communication between the paranasal sinuses and the nasal cavity was created during surgery, it was possible to examine the paranasal sinuses endoscopically 6 weeks after surgery without trephination into the paranasal sinuses. Fenestration of the conchal sinuses into the nasal cavity is usually accompanied by severe hemorrhage, but when this procedure is performed in standing horses, hemorrhage appears to be much diminished. This may be a consequence of better venous return from the nasal cavity and sinuses in standing horses, resulting in less pooling of blood in the conchal venous sinuses.27
Results of both a cryptococcal antigen enzyme immunoassay and a latex agglutination assay performed on serum samples from the horse of this report were negative even though Cryptococcus infection of the paranasal sinuses was evident on the basis of findings of cytologic examination of nasal exudate samples and histologic examination of excised tissue. This indicates that a negative result for either of these tests does not preclude a diagnosis of cryptococcosis. Detection of capsular antigen in either serum or CSF samples has been a reliable diagnostic tool in humans, cats, and dogs with a sensitivity of 90% to 100% and a specificity of 97% to 100%.12,28 To the our knowledge, there are no reports of the sensitivity or specificity of Cryptococcus capsular antigen detection in samples of serum or CSF from horses affected with cryptococcosis. Given the outcome in the horse of this report, it appears that treatment of a horse with cryptococcosis of the paranasal sinuses by surgical removal of the granulomatous lesion and oral and topical administration of antifungal drugs may be effective in eliminating the disease. Removal of the lesion from the paranasal sinuses in a standing sedated horse reduces the risk and expense of general anesthesia,27,29 and removal of a large portion of the conchae during surgery allows follow-up rhinoscopic evaluation of the paranasal sinuses. The only known complication of fenestration of a concha into the nasal cavity is a chronic, low-grade, serous nasal discharge in some horses.e
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