Diseases of the Nose and Sinuses

Symposium on Respiratory Diseases

Diseases of the Nose and Sinuses Alan M. Norris, D.V.M.,* and Elizabeth]. Laing, D .V.M.t

ANATOMY AND PHYSIOLOGY The upper respiratory tract extends from the external nares to the glottis and is made up of the nasal cavity, paranasal sinuses, and nasopharynx. The nasal cavity is the most frequent site of disease in the upper airway and it extends from the nares to the choanae (caudal openings of the nasal cavity). The nasal cavity is enclosed either by bone or cartilage and is divided in half by the nasal septum. Within the nasal cavity are a number of delicate, scroll-like structures that are referred to as chonchae (rostral nasal cavity) and turbinates (caudal nasal cavity). This complex architecture serves to increase the surface area of the nasal passages, thus enhancing the main functions of olfaction, filtration, humidification, and warming. The nasal cavity is lined by ciliated pseudocolumnar epithelium and is richly supplied with blood vessels and nerves in addition to serous and mucous glands. The area of olfaction is located on the ethmoturbinates, caudal nasal septum, frontal sinus·, and part of the bony nasal cavity that has a specialized neuroepithelium that gives rise to the olfactory nerves. 34 Both dogs and cats have a highly developed sense of olfaction that has a role in protection, behavior, and appetite. In animals with severe nasal disease, anorexia may result owing to their inability to smell food. The nose also has a filtration role and removes large particulate matter such as dust, pollens, and bacteria. The mucous secretions trap these particles, which are then moved via ciliary action to the oropharynx, where they are swallowed, or to the external nares. The air is warmed and humidified in the nose to protect the lower airway from extremely dry or cold air. The paranasal sinuses have a questionable function in the normal animal, although they are clinically important in disease states. The paranasal sinuses of the dog include the frontal sinus, maxillary recess (or sinus), *Diplomate, American College of Veterinary Internal Medicine; Staff Internist, The Veterinary Referral Clinic of Toronto, Toronto, Ontario, Canada tResident in Small Animal Surgery, Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada Veterinary Clinics of North America: Small Animal Practice-Vol. 15, No. 5, September 1985

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and the sphenoidal sinus. The maxillary recess is not enclosed in the maxilla; hence, it is not a true sinus. 34 In the cat, there are the frontal and sphenoidal sinuses. HISTORY

A thorough history is essential in differentiating upper and lower respiratory tract disease. The history should be objective, precise, and accurately document the course of the disease. The common clinical signs of upper respiratory tract disease include one or more of the following: nasal discharge, epistaxis, sneezing, facial deformity, pawing at the face, respiratory stertor, open-mouth breathing, and inspiratory dyspnea (Table 1). The clinician must be able to integrate the patient signalment, environmental history, past history, and current history to localize the problem to the upper respiratory tract. Information about when the problem was first noticed, whether it has been progressive, the medications that have been dispensed, and the effectiveness of those medications should be recorded in the history. When animals are presented because of a nasal discharge, it is important to determine if the discharge is unilateral or bilateral, acute or chronic, and to ascertain the nature and amount of discharge. An acute, unilateral nasal discharge associated with pawing at the face and sneezing is suggestive of a foreign body, whereas a chronic nasal discharge that was initially unilateral but has now become bilateral and sanguineous is indicative of a nasal tumor or mycotic rhinitis. When irritated, the nasal mucosa will initially respond with an increased serous discharge. As the disease becomes more chronic, the discharge will become mucoid and eventually purulent as the bacteria colonize and invade the nasal mucosa, resulting in tissue destruction. This discharge may be further modified by medical therapy. Acute epistaxis is most commonly due to trauma or a bleeding disorder, whereas chronic epistaxis is usually due to an invasive intranasal lesion (nasal tumor or mycotic rhinitis). Stertorous breathing is due to nasal or pharyngeal disease and suggests obstruction of the upper airways. It may be more apparent when the animal is at sleep and the owners will report that their pet is snoring. If the nasal cavity is completely obstructed, open-mouth breathing results. The "reTable I. Clinical Signs of Upper and Lower Respiratory Tract Disorders UPPER RESPIRATORY TRACT

LOWER RESPIRATORY TRACT

Nasal discharge Epistaxis Sneezing Stertor Stridor Open-mouth breathing Pawing at the face Coughing Inspiratory dyspnea Fetid breath

Dyspnea Tachypnea Coughing Exercise intolerance Fever Gagging

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verse" sneeze is a short, rapid inspiratory effort that is an attempt to clear the nasopharynx of obstructing material. Sneezing is a common sign in nasal disease and is a normal reflex to irritants. It is more frequently observed in acute diseases such as foreign bodies, allergic rhinitis, and viral diseases of cats. Although it can occur in some chronic conditions such as chronic sinusitis, it is less frequent in obstructive nasal disease. If the sneezing is paroxysmal and severe in nature, then epistaxis may result. PHYSICAL EXAMINATION

A complete physical examination should precede any special diagnostic procedures such as rhinoscopy or skull radiographs. Abnormalities are usually confined to the nasal cavity and sinuses, reflecting the localized nature of upper airway disease. The physical examination may detect other diseases in their preclinical state (that is, congestive heart failure), which may modify the diagnostic approach. When observing the patient's respiration, lateral movement of the nasal alae should occur with each inspiration. The patency of the nasal cavity is assessed by holding a clean glass or stainless steel surface in front of the nostrils and evaluating the area of condensation. Excoriation of the nasal philtrum is observed in chronic nasal discharge. A description of the nasal discharge should include information on the volume, color, and odor of the discharge. The odor of the breath should also be noted. The eyes should be inspected for epiphora resulting from obstruction of the nasolacrimal ducts (Fig. 1), exopthalmos, and increased pressure due to retrobulbar masses. Systemic infections with Cryptococcus neoformans may be manifested as a retinitis that could be detected on fundic examination. Palpation of the soft tissue and osseous shell of the nose may detect areas of pain, swellings, or masses and bony defects (Fig. 2). The muzzle should be symmetric. Most dogs will allow the clinician to examine the hard and soft palate, tonsils, and dental arcade without sedation. Occasionally, the dog may be in pain and resent palpation. Oral growths, erosions, and discharges may be noted. Percussion and auscultation of the nasal passage and sinuses can be performed, but they are limited to large dogs.

Figure 1. Cat with epiphora due to obstruction of the nasolacrimal duct resulting from a nasal carcinoma.

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Figure 2. Massive facial deformity in a 9-year-old Collie cross resulting from an osteosarcoma of the nasal cavity.

DIAGNOSTIC PROCEDURES Radiographic Examination In animals with a history of chronic nasal and/or paranasal sinus disease, radiology of the skull is a simple and effective method for determining the presence of a lesion in the nasal cavity. 13 · 17 Furthermore, the extent of the lesion can be assessed and the ideal location and method for obtaining a biopsy may be selected using radiology. Although the radiographic appearance of the lesion may allow the clinician to categorize the disease into neoplasia, mycotic (destructive) rhinitis, and inflammatory (hyperplastic) rhinitis, 13 • 17 the diagnosis should ultimately be based on cytologic and histologic appearance of specimens, in conjunction with the culture results and serology. Treatment based on radiographic appearance alone is not advisable owing to errors in diagnosis. It is essential that proper postioning and high-quality radiographs be obtained, especially in those cases of relatively short duration (that is, 1 to 2 months), in which the radiographic changes may be minimal. All animals should be under general anesthesia for proper positioning during the radiographic examination. Fine detail, nonscreen film, and proper exposure techniques will enable the veterinarian to obtain the high-quality radiographs that are essential in diagnosis. 13 • 29 Radiology should precede rhinoscopy, culture, and biopsy procedures, for the resultant hemorrhage may obscure subtle lesions and result in an increased radiopacity.

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A complete radiographic study of the nasal cavity and sinuses includes lateral, intraoral (occlusal), dorsoventral or open-mouth ventrodorsal, and rostrocaudal (skyline) frontal sinus projections (Figs. 3 to 5). Occasionally, oblique views of the skull are required to visualize the dental arcade and reduce the superimposition of skull structures that is inherent in a lateral projection. An occlusal radiograph or open-mouth ventrodorsal projection of the skull (see Fig. 3) has proved to be most useful. 13· 35 This view allows the clinician to assess the trabecular pattern, increased lucency or opacity of the nasal cavity, and whether the vomer bone is intact. 16 The patient is easier to position using an occlusal projection and the radiographic beam does not have to be directed caudally, as in the open-mouth ventrodorsal projection. By placing the corner of the radiographic plate in the animal's mouth, the caudal part of nasal cavity can be visualized. Positive-contrast rhinography has been described using unilateral intranasal administration of 30 per cent aqueous barium sulfate suspension. 14 · 15 This technique enhanced the radiographic appearance of the nasal cavity, nasopharynx, and paranasal sinuses in normal dogs . When used in dogs affected with nasal and paranasal sinus disease, it yielded information not provided by survey radiographs. 15 Rhinoscopy Direct visualization of the nasal cavity is possible using a number of instruments. Because the nasal mucosa is very sensitive, rhinoscopy must be performed with the animal under general anesthesia. Failure to employ

Figure 3. A, Line drawing demonstrating positioning of a dog for occlusal radiographs of the nasal cavity. (From Ettinger, S. J. (ed.): Textbook of Veterinary Internal Medicine. Philadelphia, W. B. Saunders <:;o., 1983, pp. 694-695; with permission.) B, Occlusal radiograph of the nasal cavity of a normal dog.

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Figure 4. A, Line drawing demonstrating positioning of a dog for ventrodorsal radiographs of the nasal cavity. (From Ettinger S. J. (ed.): Textbook of Veterinary Internal Medicine. Philadelphia, W. B. Saunders Co., 1983, pp. 694-695; with permission.) B, Ventrodorsal radiograph of the nasal cavity of a normal dog.

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Figure 5. A, Line drawing demonstrating positioning of a dog for a frontal sinus or rostrocaudal radiograph. (From Ettinger, S. J. (ed.): Textbook of Veterinary Internal Medicine. Philadelphia, W. B. Saunders Co. , 1983, pp. 694-695 with permission.) B, Frontal sinus radiograph of a normal dog.

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Figure 6. Rigid 2.7-mm endoscope used for examining the nasal cavity.

a surgical plane of anesthesia will prevent adequate examination of the nasal cavity, and will often result in nasal trauma and damaged instrumentation. There are a number of limitations when performing rhinoscopy. The technique is limited to medium or large dogs because of the size of the instrumentation and the well-developed and convoluted turbinates that prevent passage of the scope. The copious amounts of mucus often present in nasal disease may obscure vision, and suction often has to be used during the procedure. An 8 French urinary catheter is ideal if the secretions are not too tenacious. The last obstacle facing the endoscopist is that, in the diseased state, the nasal cavity is prone to bleeding, which can further obscure vision. Patience, perseverance, and practice are essential traits a clinician must have when doing rhinoscopy. An otoscopic speculum and light handle can be effective in examination of the rostral rhinarium but is inadequate to visualize the turbinates. Because most neoplasms and many mycotic lesions occur in the caudal half of the nasal cavity, these lesions will be missed. A rigid 2. 7-mm endoscope* has enabled the authors to examine the entire nasal cavity from the nares to the nasopharynx (Fig. 6). The nasopharynx and choanae may be readily examined using a nasopharyngeal illuminator and mirrors that attach to a standard otoscopic light handle. The soft palate must be pulled forward with tissue forceps, allowing the nasopharynx to be visualized. The mirrors and light sources should be warmed or an antifogging agent applied to retard condensation forming on the reflecting surface. The use of 4- to 6-mm flexible fiberoptic endoscopest has been described for caudal rhinoscopy. 39 • 48 The normal nasal mucosa is a shiny, pink color with minimal serous discharge. Mycotic lesions are most readily identified, for they have a distinctive appearance and the nasal turbinates are atrophied, making passage of the endoscope easy. The white, fluffy plaques can be seen on the nasal mucosa. Visualization of tumors is more difficult owing to excessive mucus, hemorrhage (much of which is iatrogenic), and physical obstruction within the nasal cavity. Culture

The nasal cavity of the normal dog harbors a wide variety of microorganisms that are often present as a mixed bacterial and fungal population. Streptococci, staphylococci, E. coli, Pseudomonas sp., and Proteus sp. are all normal inhabitants of the nasal cavity, and a bacterial culture of the nose or nasal discharge is often positive, yielding a mixed bacterial population. In animals with nasal and/or paranasal sinus disease, a pure heavy growth *Karl Storz GMBH & Co., Tuttlingen, West Germany. tOiympus BF-2TR Bronchoflberscope. Olympus Corp., New Hyde Park, New York.

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of an organism may be important. Sensitivity testing is ot most importance when purulent nasal discharges develop postoperatively and the bacteria may be a resistant noscomial infection. Fungal culture is more rewarding than bacterial culture, and a positive culture in a symptomatic dog is significant. Aspergillus sp. and, more recently, Penicillium sp. are the fungi isolated, although both these organisms occur in 30 to 40 per cent of normal dogs or dogs with nasal tumors . 18• 19 Failure to isolate fungi in positive cases of aspergillosis or penicilliosis may be due to poor sampling technique, bacterial overgrowth, or poor culture technique. Serology The agar gel diffusion test is a serologic test available for detecting Aspergillus sp. or Penicillium sp. 19• 24 • 25• 42 It is available in many veterinary teaching hospitals and public health laboratories. Based on recent work by Harvey that has identified Penicillium sp. in fungal rhinitis, it is advisable to test for both Aspergillus sp. and Penicillium sp. False negatives are rare except in the early course of the disease, and these will usually seroconvert later. Animals with other nasal diseases, such as neoplasms, may be serologically positive owing to a concurrent fungal infection. 25 Biopsy Procedures There are a variety of methods to collect tissue samples from animals with nasal and paranasal sinus diseases. If a palpable mass is present, the simplest technique is direct fine-needle aspiration or punch biopsy of the mass. For intranasal lesions, a variety of techniques have been described for nasal flushing and tissue sample collection. 3 1. 55 All of them are done with the animal under general anesthesia and in lateral recumbency with the affected nasal cavity most ventral. Plastic tubing is then inserted into the nasal cavity either through the external nares or nasopharynx to allow saline to be flushed through the nose. Flushing via the external nares is the easier technique. A 6 or 8 French male urinary catheter or a plastic 14-gauge intravenous catheter is suitable for insertion via the external nares. The plastic tube can be bevelled at a 45° angle to create a sharp cutting edge, although this is not essential. The distance from the external nares to the medial canthus is measured, and the appropriate length of tubing cut. If the plastic tube extends past the medial canthus, penetration of the cribriform plate is possible. Aspiration of fluid and tissue is prevented by using an endotracheal tube with an inflatable cuff and packing off the oropharynx with gauze. The table should be tilted so that the nasal flush flows out the external nares . By placing gauze squares under the nose, fragments of tissue may be collected. A 35-cc syringe is filled with sterile physiologic saline, and vigorous flushing action is obtained by applying alternate positive and negative pressure. Aliquots of 5 to 10 cc of saline are introduced into the nasal cavity as the catheter is vigorously withdrawn and inserted against the turbinates. It is essential to be aggressive in an attempt to dislodge tumor fragments, bits of bone, and cores of tissue. The tissue dislodged will be caught in the gauze squares or the syringe. 55

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Figure 7. A biopsy needle used for acquiring tissue samples in obstructive nasal disease.

In obstructiye nasal disease when lesions are visible on radiographs, a Tru-cut* biopsy needle may be used (Fig. 7). The distance and location of the lesion and the area for insertion of the biopsy needle must be determined from radiographs. A diagnostic tissue sample may not be obtained when mucinous carcinomas are present or in mycotic rhinitis when the turbinates are atrophied. 38 Rhinotomy and Turbinectomy Exploratory nasal surgery is used to both diagnose and treat intranasal disease. Surgical exploration of the nasal cavity is used to obtain diagnostic biopsies in cases in which other diagnostic procedures have been unrewarding. Nasal surgery is also used to treat cases unresponsive to medical therapy, remove foreign bodies or necrotic debris, and debulk tumors prior to adjuvant therapy. The technique of rhinotomy and turbinectomy has been described. 8 • 20• 29 ACUTE DISEASES OF THE NASAL CAVITY AND SINUSES Trauma Injury to the nose is most commonly the result of blunt trauma (a motor vehicle accident or collision with a fixed object); rarely, it is the result of penetrating trauma (as occurs with dog fights, bullet wounds, or impalement by a stick). The immediate result is usually epistaxis, which frequently causes the owner more concern than the dog or cat. The history and physical examination are usually sufficient to establish that the epistaxis is a result of trauma. The entire skull and oral cavity should be examined for displacement fractures or malalignment of the facial bones. The patient should be closely observed for neurologic signs resulting from concurrent cranial trauma. Skull radiographs are usually delayed until the patient is stabilized. In an attempt to control hemorrhage, the patient is initially treated with cage rest and close observation. Unfortunately, many animals are anxious immediately after the trauma and the concurrent upper-airway obstruction may result in an animal that could further traumatize its nose.

*Tru-Cut Disposable Biopsy Needle. Travenol Laboratories, Inc., Deerfield, Illinois.

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Sedation with a narcotic, such as Demerol or oxymorphone, * will calm the fractious patient and may result in mouth breathing, which is a desirable effect. If epistaxis is copious, the patient's head should be kept lower than the body to prevent aspiration of blood. Applications of external ice packs to the dorsum of the nose only add to the animal's distress and are not usually effective in controlling hemorrhage. Packing the external nares is of little value, for blood continues to be lost through the internal nares. The clinician may falsely believe that the hemorrhage has stopped while, in actuality, blood is being swallowed. In addition, the blood may be unable to drain out the nose and could further obstruct the oropharynx. If the bleeding is persistent or severe, the vital signs and packed cell volume should be monitored. Fluid therapy and instillation of whole fresh blood should be initiated as the hematocrit falls. Instillation of dilute epinephrine (1:100,000) into the affected nasal cavity will cause vasoconstriction and help control hemorrhage. A 5 per cent solution of cocainet sprayed intranasally will cause local anesthesia and vasoconstriction and may be more effective than epinephrine. If this fails to control the bleeding, the patient should be anesthetized and a cuffed endotracheal tube inserted. After the larynx, pharynx, and nasal cavity are cleared of frank blood and clots of blood, the internal and external nares are packed with gauze bandage. These can be removed 24 hours later if the hemorrhage has ceased. Rarely, surgical exploration may be required to remove the damaged turbinates, bone fragments, and control hemorrhage. A consequence of nasal trauma could be obstruction of the nasal cavity. Acutely, this is the result of hemorrhage, mucosal edema and inflammation, and malaligned bone fragments. If the animal can breath through its mouth, a conservative approach to therapy is patient stabilization, maintenance of vital signs, and control of epistaxis. The obstruction will resolve as the blood clots and hemorrhage and inflammation subside. Antibiotics are indicated to prevent infection of damaged nasal tissues. If sprayed intranasally, an alpha adrenergic sympathomimetic such as ephedrine:j: or phenylephrine§ will cause vasoconstriction and subsequent decongestion. In severe obstruction when mouth breathing is inadequate, a tracheostomy may be needed to maintain ventilation. If there is persistent nasal obstruction, a rhinotomy may be necessary to remove the damaged turbinates and bone fragments . All damaged or devitalized tissues must be removed if chronic nasal disease is to be avoided. Bone without its periosteal attachment should be removed, for it will result in sequestra formation . If there are severely displaced bone fragments impinging on the nasal cavity, these should be realigned and fixed with wires or pins. Potential sequelae to nasal trauma include osteomyelitis (bacterial or fungal), sequestra formation, sinusitis, and frontal mucocele formation.

*Numorphan. DuPont Canada Inc., Mississauga, Ontario, Canada. tCocaine. Allen & Hanburys, Toronto, Ontario, Canada. :j:Allen & Hanburys, Toronto, Ontario, Canada. §Neosynephrine. Sterling Products, Aurora, Ontario, Canada.

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Figure 8. Lateral radiograph of a 6-year-old Airedale with osteomyelitis (arrow) of the frontal bones. The dog had chronic rhinitis, sinusitis, and a mucocele.

Foreign Bodies The natural curiosity of dogs in conjunction with their well-developed sense of smell result in a variety of foreign bodies (grass awns , foxtails, and porcupine quills) being inhaled or lodged in the nasal cavity (Figs. 8 and 9). Sadistic individuals may place foreign objects in the nose or, more commonly, fire bullets from rifles or hand guns at dogs (Fig. 10). Foreign bodies in the nasal cavity are rare in cats. Dogs with foreign bodies present acutely distressed, often pawing at their face and sneezing. Epistaxis may be the direct result of the foreign body or a sequel to the paroxysmal sneezing. The diagnosis of a foreign body can be difficult if the foreign body is radiolucent. The history and acute presentation are often the basis upon which a diagnosis is made. The presence of additional porcupine quills or a recent history of quill removal may point to an occult porcupine quill lodged in the nose. A thorough examination of the oral cavity may reveal the port of entry of a stick or projectile that has lodged in the nose. In acute cases, the sneezing and excessive nasal discharge may dislodge the foreign body. More often, rhinoscopy is needed to visualize the foreign material and will enable the clinician to remove it with forceps. If the foreign object cannot be identified, a therapeutic nasal flush (see the section "Biopsy Procedures") can be done in an attempt to dislodge it. The nasal flush must be vigorous if it is to be beneficial. The material collected should

Figure 9. A, Occlusal radiograph of a 2-year-old Lhasa Apso with increased density (arrow) in the left nasal cavity. (Courtesy of Dr. Paul Pennock, University of Guelph. ) B, Juniper twig removed from the nasal cavity. (Courtesy of Dr. Paul Pennock, University of Guelph.)

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Figure 10. An occlusal radiograph demonstrating radio-opaque buckshot in a 2-year-old Labrador Retriever . .

be thoroughly screened in an attempt to identify the plant material or foreign body. A course of antibiotics are administered to prevent bacterial rhinitis. Animals are monitored to ensure that chronic nasal disease does not develop. If it does, then surgical exploration and curettage of the nasal cavity are needed to try to identify the foreign body. Epistaxis The acute causes of epistaxis are trauma, presence of a foreign body, and a bleeding disorder. The reader is referred to the previous sections for information on trauma and foreign bodies. The coagulopathies that can result in epistaxis are numerous and include von Wille brand's disease, hemophilia, disseminated intravascular coagulation, or multiple myeloma, to name a few. In bleeding disorders, epistaxis is the only sign referable to the nasal cavity; no concurrent nasal discharge or sneezing is reported. Other clinical signs may reflect the underlying disease process and the systemic nature of the disease. Acute Inflammatory Diseases Acute inflammatory diseases of the upper respiratory tract are most frequently a result of a viral infection. In the cat, a number of etiologic agents are involved in causing upper respiratory disease, with the most important agents being feline herpesvirus and feline calicivirus. A number of viruses have been identified as having the capacity to cause upper respiratory disease in the dog. These include canine distemper

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virus, canine adenovirus type 1 and type 2, canine parainfluenza, and, rarely, reovirus or herpesvirus. Secondary bacterial rhinitis is common following the primary viral infection. A wide variety of aerobes (Staphylococcus sp., Streptococcus sp., E. coli, Bordetella bronchiseptica) and anaerobes form the normal microflora of the nose and could be pathogens. Primary bacterial rhinitis in the dog and cat is rare. For a complete description of the viruses of the upper respiratory tract, the reader is referred to the article "Infectious Respiratory Diseases." CHRONIC DISEASES OF THE NASAL CAVITY AND SINUSES Chronic Inflammatory Rhinitis/Sinusitus The patient with chronic inflammatory disease of the nasal cavity is both a diagnostic and therapeutic challenge to the clinician. Unfortunately, despite extensive efforts to establish a definitive diagnosis and to administer adequate therapy, many animals continue to have chronic signs of nasal disease· this becomes a frustration for the client, patient, and veterinarian. Although certain features of the patient signalment, history, orphysicai examination may lead the clinician to suspect a particular disease process, it is often not possible to categorize chronic nasal disease into a neoplastic process, mycotic infection, or chronic rhinitis with reliability. A geriatric dog with a unilateral nasal discharge, periodic epistaxis, and facial deformity most likely has a nasal tumor, but a definitive diagnosis is needed before specific therapy can be initiated. For this reason, it is advisable to do a complete evaluation of the patient relatively early in the course of the disease, rather than administer a wide range of symptomatic treatments. The decision to proceed with diagnostic tests is dependent on a variety of factors, including whether there has been previous treatment, the nature of the therapy, and response to that therapy. The owner's desire for a definitive diagnosis and the veterinarian's confidence in his or her ability to diagnose the condition will temper the decision to be aggressive diagnostically. A nasal discharge of many months' or years' duration that was initially unilateral and is now bilateral and that may be serous, mucoid, purulent, or sanguineous is typical of the patient with chronic rhinitis. Additional signs that owners report include paroxysmal sneezing, ocular discharge secondary to nasolacrimal duct obstruction, and gagging or retching due to postnasal drip. Tonsillitis or pharyngitis may be secondary to the rhinitis. The clinical signs usually respond transiently to antibiotics, often changing a purulent nasal discharge to one that is mucoid in character. The clinical signs recur shortly after the medication is stopped. In dogs, previous history of a motor vehicle accident with head trauma, or exposure to a porcupine may precede the development of a chronic nasal discharge. In cats, it is more frequent to have a history of an acute viral infection of the upper respiratory tract that initially responded to symptomatic therapy but that has now developed into chronic rhinitis/sinusitis. Most often there is no precipitating cause or isolated event that can be associated with the development of clinical signs.

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Figure 11. Occlusal radiograph of a 2-year-old Labrador Retriever with chronic rhinitis. There is a mild increase in density of the nasal cavities due to the excessive secretions and hyperplasia of the nasal mucosa.

The radiographic features of chronic rhinitis are increased density of the nasal cavity due to excessive secretions and hyerplasia of the nasal mucous membranes (Fig. 11). Typically, the turbinates are not destroyed unless the disease is advanced, the vomer bone is rarely eroded, and the frontal sinuses do not have increased radiopacity. 13• 17 If these latter signs are present, then a nasal tumor should be suspected (Table 2). Evidence of malaligned facial bones or excessive formation of new bone may indicate Table 2. Radiographic Changes in 98 Dogs with Intranasal Disease* INFLAMMATORY TUMORS (% OF RADIOGRAPHIC CHANGES

Loss of trabecular pattern Increased opacity Mixed density Increased lucency Vomer bone destruction Soft tissue swelling Facial bone destruction Frontal sinus opacification

CASES)

98 40 58 0 32

40 42 78

50

(HYPERPLASTIC

MYCOTIC (DESTRUCTIVE

CONDITIONS) (% OF 22 CASES)

RHINITIS) (%OF 26 CASES)

0 100 0 0 0 0 0 14

100 0 11

88 7 0

7 11

*Adapted from Gibbs, C., et al.: Radiological features of intra-nasal lesions in the dog: A review of 100 cases. J. Small Anim. Pract., 20:515-535, 1S79.

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a fracture as the precipitating cause . When chronic rhinitis is suspected, oblique views of the skull should be taken to evaluate the upper dental arcade. Root abscess of the upper canine tooth can cause a unilateral nasal discharge if the abscess extends into the nasal cavity. An abscess of the root of the carnassial tooth can also manifest as a chronic nasal disease because it borders on the maxillary recess. Culture and sensitivity testing of the nasal discharge usually yields a mixed population of anaerobes and aerobes of questionable pathogenicity. Pure cultures of bacteria are occasionaly isolated. A vigorous nasal flush (as described earlier) will usually yield material that can be submitted for cytology and histology. The diagnosis of chronic rhinitis is a diagnosis of exclusion, having ruled out nasal tumors and mycotic rhinitis. Exploratory surgery may be necessary to differentiate chronic rhinitis from neoplasia or a fungal infection. At the time of surgery, a biopsy is obtained, the diseased nasal turbinates removed, and tubing may be inserted for long-term flushing. a. 20 Conservative management of chronic rhinitis would include the administration of the following : l. Broad-spectrum antbiotics administered for 3 to 6 weeks. There is no evidence that topical nasal antibiotics have an advantage over systemic therapy, so we initially administer antibiotics orally, because most owners find this route of administration easier. Chloramphenicol and tetracycline have proved effective. 2. Nasal decongestants administered either topically or systemically. Decongestants are alpha adrenergics and they cause constriction of the arterioles of the nasal mucosa, thereby reducing nasal congestion and edema due to decreased blood flow to these tissues. The result is improved airflow, increased drainage, and decreased production of secretions. 10• 11 Available intranasal preparations include phenylephrine hydrochloride* or xylometazolinet . Systemic preparations of phenylpropanolamine* are also available ; Rebound congestion occurs after prolonged use of decongestants and can be minimized by using the drugs for only 3 to 4 days at a time. 11 • 39 3. Corticosteroids, if an allergy was the basis of the upper respiratory disease. The finding of an increased number of eosinophils in the nasal discharge or circulation would support the diagnosis of allergic rhinitis. Prolonged use of corticosteroids could cause shedding of virus in a carrier cat infected with feline rhinotracheitis/feline calicivirus, predispose a patient to mycotic rhinitis, or allow existing mycotic rhinitis to disseminate. Therefore, corticosteroids should be used with caution.

More aggressive therapy may be needed, for conservative management is often unsuccessful. In the same manner that a diagnostic nasal flush is performed to obtain tissue samples (see the section "Biopsy Procedures"), a therapeutic nasal flush can be done with 10 to 20 ml of providone-iodine solution§ diluted 1:10 with saline. The nasal discharge will usually decrease or stop completely after this treatment, but often recurs in a few months. Finally, surgical exploration may be needed to remove diseased turbinates, bone fragments, foreign bodies, and collect additional biopsies. Insertion *Neosynephrine. Sterling Products, Aurora, Ontario, Canada. tOtrivin. CIBA Pharmaceuticals, Mississagua, Ontario, Canada. :j:Ornade. Smith Kline and French Canada Ltd., Mississauga, Ontario, Canada. §Betadine Solution. Purdue Frederick Inc., Toronto, Ontario, Canada.

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Figure 12. A, Necropsy specimen of a 9-year-old dog with an adenocarcinoma of the nasal cavity and frontal sinus. B, Necropsy specimen of a dog with an adenocarcinoma of the nasal cavity and frontal sinus.

of drains into the frontal sinus will allow postoperative flushing of the sinus and nasal cavity for 7 to 14 days. An iodine solution is an excellent antiseptic to use for this purpose. Nasal and Paranasal Sinus Tumors Canine nasal and paranasal sinus tumors are not uncommon, with an incidence of 1 to 2.5 per cent of all reported neoplasms.32 • 43 This number probably underestimates the tnfe frequency of the disease because of the owner's reluctance to subject their pet to the necessary diagnostics and the difficulty in establishing the diagnosis. Among domestic animals, the dog has the highest incidence of nasal tumors (Fig. 12), followed by the cat (Fig. 13). 27. 32 The tumor occurs in dogs that are usually more than 8 years of age. 31 • 32 · 37 Dolichocephalic breeds are at a higher risk of developing nasal carcinoma than brachycephalic breeds. 22 Specifically, the Airedale Terrier, Basset Hound, Old English Sheepdog, Scottish Terrier, Collie, Shetland Sheepdog, and German Shorthaired Pointer are at the highest risk. 22 Why dolichocephalic dogs have an increased incidence of nasal tumors is not clear. The increased surface area and filtering capacity of the nose has been the hypothesized explanation, 46 although certain long-nosed breeds (Doberman Pinschers, for example) are at a lower risk for developing nasal

Figure 13. Necropsy specimen of a mature cat with an adenocarcinoma of the nasopharynx.

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tumors . 22 Brachycephalic breeds commonly mouth-breath owing to upper airway obstruction and may have a reduced exposure to airborn carcinogens, thus accounting for the reduced risk in this group of dogs. No association between nasal tumors and environmental carcinogens has been established. 46 Tumor involvement of the paranasal sinuses occurs more frequently in the dog than in the cat. 32 Regardless of location of the tumor, the overwhelming majority of nasal tumors are malignant. 32 · 43 The complex structure of the nasal cavity is reflected in the types of tumors encountered. Adenocarcinomas, unspecified carcinomas, and squamous cell carcinomas are the common epithelial tumors; fibrosarcomas, chondrosarcomas, and osteosarcomas are the common mesenchymal tumors reported. 19• 22 • 35 • 43 Metastases from nasal carcinoma occur in about 10 per cent of cases and in the latter stages of the disease. Common sites of metastatic involvement are the lymph node, brain, and lung. It has been suggested that sarcomas are less likely to metastasize. 22 The clinical findings in animals with nasal tumors are nonspecific and could be attributed to chronic rhinitis or mycotic rhinitis. A unilateral discharge that may be mucoid or purulent but is most often sanguineous is the usual presenting complaint. Severe, periodic epistaxis is common. A large proportion of the dogs sneeze and have marked respiratory stridor. As the disease progresses, facial deformity, ocular discharge, exophthalmos,

Figure 14. Occlusal radiograph of a 10-year-old dog with a nasal adenocarcinoma. There is destruction of the vomer bone (arrow), a loss of the turbinate trabecular pattern, and a large cystic lesion.

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and oral growths are clinical signs that develop and enable the clinician to specifically diagnose the nasal tumor. 31 · 32• 37 Animals have usually received extensive medical therapy prior to a definitive diagnosis being made. An occlusal radiograph is the most useful view in evaluating nasal disease. 13• 17 • 35 Radiographic features seen in a high number of nasal tumors include loss of the turbinate trabecular pattern (Fig. 14), erosion of the vomer bone (Fig. 15), increased radiopacity of the nasal cavity and frontal sinus (Fig. 16), destruction of the overlying facial bones (Fig. 17), and an external mass (see Table 2). 13· 17 Radiographic differentiation of nasal tumors from chronic rhinitis and mycotic rhinitis can be difficult and may result in errors. An accurate diagnosis is dependent on obtaining adequate tissue for cytology and histopathology. A Tru-Cut biopsy needle, nasal flush, or surgical exploration can all yield diagnostic material if properly employed. 31 · 28 · 55 If noninvasive techniques fail to produce adequate tissue, surgical exploration allows one to obtain a definitive diagnosis. 20 • 29 Surgery has historically been the treatment of choice for nasal tumors, despite numerous reports that have stated that survival times are not improved following surgery. 6 · 32• 37 Because complete removal of the tumor is rarely possible owing to invasion into the bone, especially in the area of the cribriform plate and orbit, recurrences are the rule. There is increased morbidity associated with surgery that results from blood loss, anesthetic complications, or brain injury. Finally, surgery may result in hypoxia of the

Figure 15. An occlusal radiograph of a Golden Retriever with multiple cystic lesions (white arrow) in the nasal cavity and erosion of the vomer bone (black arrow).

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Figure 16. Occlusal radiograph of a 2-year-old Irish Setter. There is increased radiopacity of the nasal cavity with a loss of the turbinate trabecular pattern (arrow).

Figure 17. Lateral radiograph of a dog demonstrating erosion of the frontal bone due to tumor invasion (arrow).

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residual tumor that can result in resistance to radiation therapy. Therefore, surgery should be viewed as a diagnostic tool or as an adjunct to radiation therapy but can no longer be considered the treatment of choice. Cryosurgery in the treatment of nasal tumors does not seem to improve survival. 32· 37 · 56 A theoretical advantage of cryosurgery is that residual neoplastic cells in the bone are destroyed. The dead bone can then serve as a graft, eventually becoming revascularized. Application of the cryogen in the nasal cavity is difficult and may result in oro nasal fistulas . 56 Because it does not offer significant advantages over scalpel excision, it is no longer advocated for the treatment of nasal tumors. Radiation therapy is being evaluated as an adjunct to surgery and as a primary treatment modality for nasal tumors. In 21 dogs with nasal tumors, treatment consisted of surgical debulking followed by radiation therapy. The source of radiation was an orthovoltage x-ray therapy machine (a total dose of 26 to 45 Gy was administered). The mean and median survival times were 25 and 23 months, respectively. One-year survival rate was 57 per cent, and 2-year survival rate was 48 per cent. The results of this study clearly demonstrate that surgical deulking followed by radiotherapy is clearly superior to surgery alone. 50 Unanswered questions include whether high-energy radiation in the form of cobalt or megavoltage x-ray is superior to orthovoltage x-rays, the value of surgical debulking before radiotherapy, the optimal dose of radiation needed, and the response of various types of tumors to radiation. 50 Recommendations for the future will be based on the answers to these questions; it is clear, however, that radiation is the treatment of choice. Mycotic Rhinitis

Aspergillosis-Penicilliosis. Fungal infections of the nasal cavity and sinuses of dogs are being recognized more frequently . 19 Aspergillus sp. is the main fungal agent isolated from cases of destructive rhinitis, although recently Penicillium sp. has been reported as a pathogen. 18• 19 Aspergillosis of the nasal cavity and sinuses is extremely rare in cats .53 In man, infection with the opportunistic fungus Aspergillus sp. is usually encountered in immunosuppressed patients. 12 These patients often have debilitating disease or are receiving therapy known to suppress the immune system. Most commonly, they have a concurrent malignant disease or chronic obstructive pulmonary disease that predisposes them to pneumonic aspergillosis. 12 In dogs with nasal aspergillosis, impaired immune function has been demonstrated in a limited number of dogs. Cell-mediated (T-cell) function was defective, as assessed by lymphocyte blastogenesis, in two of three dogs with aspergillosis. 2 Disseminated aspergillosis has been reported recently; predisposing factors included prior treatment with corticosteroids or antibiotics. 36 • 57 Despite these reports, most animals with nasal aspergillosis are clinically healthy and have not received immunosuppressive treatment prior to the onset of the disease. Infection with Aspergillus sp. will also cause immunosuppression and can therefore be a primary pathogen. 19 Nasal or head trauma has been reported in many dogs that subsequently developed mycotic rhinitis, with the damage to the turbinates allowing the opportunistic fungi to invade the bone. 19

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Aspergillosis-penicilliosis infection occurs in animals of any age; this differs from nasal tumors, which occur in older animals. A wide range of breeds develop aspergillosis-penicilliosis. The Collie is reported to be affected more frequently, whereas brachycephalic breeds are rarely affected.19 The discharge is unilateral initially, but often becomes bilateral. It is typically mucopurulent, although antibiotic therapy may temporarily resolve the purulent nature of the discharge. Epistaxis or a sanguineous nasal discharge is frequently noted by the owner. Essentially, the clinical signs are identical in dogs with nasal tumors and mycotic rhinitis. Only in advanced neoplasia, where there is facial deformity or exophthalmos, can a tumor be easily differentiated from mycotic rhinitis on the basis of clinical signs. The diagnosis is based on a combination of radiology, direct visualization of the fungal plaques, culture of the organism, cytology/histology, and serology. A loss of turbinate trabecular pattern, punctate radiolucencies, and generalized radiolucency of the nasal cavity are usually seen on the occlusal radiographs (Figs. 14 to 17). 13· 17 Culture of the nasal cavity or nasal discharge is beneficial, but false negatives are not uncommon owing to bacterial overgrowth or improper specimen handling. False positives are also encountered, because aspergillosis can be isolated from the nasal cavity of 30 to 40 per cent of normal dogs or dogs with nasal tumors. 19 Rhinoscopy has proved to be an effective means of visualizing the white fungal plaques on the mucosa of the nasal cavity. Rhinoscopy is relatively easy in cases of aspergillosis owing to loss of the turbinates, which allows easy passage of the scope. Adequate material may be collected for histology and culture by a vigorous nasal flush or exploratory surgery and a biopsy. More recently, an agar gel double diffusion test has been available to identify Aspergillosis sp. and Penicillium sp. 24 • 25 • 42 False negatives are rare with this test except in early cases, which often seroconvert later in the disease. A positive result reflects infection with aspergillosis-penicilliosis but does not eliminate other diseases, such as nasal tumors that are concurrently infected with fungus. The proper management of mycotic rhinitis is unknown. A variety of therapies have been advocated, which reflects the difficulty in treating this disease. In mild cases in which there are minimal radiographic changes, medical management is used alone; in more severe cases or in cases that are unresponsive to medical therapy, surgical intervention is needed. Therapies that have been employed include the following : l. A therapeutic nasal flush that can be performed at the same time as a diagnostic nasal flush, or at a later time, is done. The technique is the same as previously described, except 10 to 20 ml of povidone-iodine solution diluted 1:10 with saline is used. This is not used as the sole method of therapy, but it is used in combination with systemic medication. 2. Thiabendazole administered orally for 6 weeks at a dosage of 20 mg per kg per day. This has been reported to be the primary treatment of choice. 19• 21 The dosage may be divided and given twice daily or administered in a single dose. A frequent side effect of thiabendazole is anorexia; vomition and diarrhea are encountered less frequently . If side effects develop, temporary cessation of the drug is advocated . The drug may be reintroduced at half the dose, and then the dose can be increased gradually until the full therapeutic level is achieved and maintained

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for 6 weeks . Although sporadic case reports indicated that treatment with thiabendazole was encouraging,'· 24 a large study of dogs with aspergillosis-penicilliosis did not support this. 21 In 47 dogs with fungal rhinitis due to Aspergillus sp. or Penicillium sp. , only 43 per cent of the animals were considerably improved following surgery, and only 26 per cent had complete cessation of clinical signs. Although thiabendazole still remains the recommended treatment, additional therapy is clearly indicated in both mild and advanced cases. 3. Other systemic medications such as amphotericin B, 5 nystatin!• 5-fluorocytosine! sodium iodide! and, most recently, ketoconazole. 1 Reports on the use of these agents in dogs is rather sporadic, and the results are confusing, especially since most dogs had received a combination of surgery, local instillation of medication, and systemic treatment. Long-term follow-up on these cases is rarely reported. As a result, no specific recommendations on the use of these agents to treat aspergillosis can be made at this time. 4. Surgical exploration and curettage of the nasal cavity and sinuses to remove the affected tissue. This therapy is indicated in dogs with obvious turbinate destruction or in which medical therapy has failed. Drains are placed into the frontal sinus, allowing daily postoperative flushing with either povidine-iodine or thiabendazole suspension at 20 mg per kg. 19

Cryptococcosis. The clinical manifestations of Cryptococcus neoformans are largely dependent on the organ system(s) involved. Most frequently, it affects the upper respiratory system, resulting in a chronic nasal discharge; lower respiratory involvement is not common. Ocular, cutaneous, and neurologic syndromes have also been reported in cryptococcosis. More than one syndrome may occur in the same animal. 52 Cats are more frequently affected with cryptococcosis than dogs . C. neoformans is a saprophytic organism that has a worldwide distribution. Exposure is via environmental contact, although it is widely believed that a deficiency in the immune system is a prerequisite to infection in many cases. In man, leukemia, lymphoma, or other malignancies are often present concurrehtly. 12 Immunosuppressive therapy also predisposes the patient to infection with C. neoformans. Cats with cryptococcosis are often positive when tested for the presence of feline leukemia virus, which is known to suppress cell-mediated immunity. 1• 28 Disease of the upper respiratory system is manifested as a chronic mucopurulent nasal discharge, sneezing, and stertorous breathing. A palpable mass is often present on the dorsum of the nose .5 2 The diagnosis is usually established by demonstrating the organism in the nasal discharge. If there is a swelling over the nose, a fine-needle aspirate or biopsy will usuaily yield diagnostic material. Feline cryptococcosis has been treated using amphotericin B40 • 49 or flucytosine 30 alone and in combination. 1• 44 • 51 It appears that combination of the two agents has an advantage in that they act synergistically and the amount of amphotericin B that has to be administered to the patient can be reduced. 23 • 33 Amphotericin B alters permeability of the fungal cell membrane and causes cellular death; 23 • 45 · 47 it also enhances uptake of flucytosine. The proper dosage schedule for amphotericin B is not known, and many different treatment regimens have been empirically suggested. It is given intravenously in 5 per cent dextrose and water. Ideally, it should be given very slowly in a large amount of the vehicle on a daily basis. This

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can be done in the dog, where .5 mg/kg/day or 1 mg/kg every other day can be given in 250 to 1000 ml of 5 per cent dextrose over 6 to 8 hours. The total dose of amphotericin B to be given is 7.5 to 8.5 mg per kg. 45 • 47 In cats, the daily administration of large amounts of fluids over a prolonged period creates restraint problems. Therefore, the drug is given in 5 to 10 ml of 5 per cent destrose over 3 to 5 minutes. A minimum of 12 treatments has been recommended. The toxic nature of amphotericin B is well documented, 45 with nephrotoxicity and hypokalemia being most important. Thus, blood urea nitrogen, creatinine, and serum potassium should be monitored. After entering the cell, flucytosine (5-fluorocytosine) becomes 5-fluorouracil, an antimetabolite that inhibits nucleic acid synthesis. Mammalian cells lack the enzyme needed to convert flucytosine and, as a result, toxicity to the patient is low. 23· 33 Primary resistance and secondary resistance following treatment is high with flucytosine, so it is not recommended that it be used alone but only in conjunction with amphotericin B.33 By using the drugs in combination, this allows one to reduce the dose of the highly toxic amphotericin B by 50 per cent. The total dosage of flucytosine is 150 mg per kg per day, orally, given in two divided doses for 6 weeks. 44 As the drug is excreted in the urine, close monitoring of the patient's renal function is imperative. The main side effect is oral and cutaneous ulcerations. Current suggestions are for combination therapy using amphotericin B and 5-fluorocytosine. Recently, ketoconazole has been reported to be efficacious in the treatment of feline cryptococcosis. 28 Ketoconazole binds to the fungal cell membrane and effects cell permeability with leakage of cell contents. The suggested dosage is 20 mg per kg in two divided doses, although the dosage is doubled if meningitis is present. 47 The optimal duration of therapy for ketoconazole is unknown, but it may need to be given for 6 months. Further clinical studies are needed before this drug can be advocated as the sole agent in the treatment of cryptococcosis or in combination with amphotericin B. Nasopharygneal Polyps. Inflammatory polypoid growths within the feline nasopharynx are not common but should be suspected in any cat with chronic upper respiratory disease. 3• 26• 41 Nasopharyngeal polyps may also cause chronic otitis media, and polyps have been observed in the external ear canal. Affected cats are of either sex and range in age from 6 months to 5 years. The clinical signs include sneezing, a nasal discharge, or stertorous respiration. Signs of otitis media are also observed and include head shaking, head tilt, nystagmus, and otorrhea. There is considerable disagreement as to the site of origin of the nasopharyngeal polyps. They enter the nasopharynx by way of the eustachian tube, but it is not certain whether they arise from the tissue of the eustachian tube or the middle ear. 3 · 4• 26 The etiology of nasopharyngeal polyps is unknown, but recently the disease has been seen in three cats from 't he same cattery, suggesting an infectious etiology. In support of this, feline calicivirus was isolated from the nasopharynx of two of these cats and directly from the polypoid tissue of one of these two cats. 41 Calicivirus should be considered as a possible etiology of inflammatory polyps in the cat.

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The diagnosis is made by examining the nasopharynx under general anesthesia. A polyp is usually seen arising from the eustachian tube, where it is attached by a stalk. Radiographs of the skull may reveal bulla osteitis. 41 The polyp is surgically removed through the oral cavity by incising the soft palate along the midline. The polyp can then be visualized and removed. The prognosis is good provdied the entire polyp and its base are removed. Reverse Sneeze. The term "reverse sneeze" is used to describe a syndrome of acute inspiratory dyspnea in the dog. Dogs are asymptomatic before and after the "attacks," but during the episodes, they have acute distress that is typified by stertor and obvious inspiratory dyspnea. The episodes are less than 1 minute in duration. The etiology is unknown, but most likely it is a result of the epiglottis obstructing the glottis, which results in acute dyspnea. The animals are usually normal upon physical examination, as is the oral cavity and nasopharynx when examined under anesthesia. There is no medical or surgical management available to prevent the episodes. During the attacks, instilling a small amount of water (2 to 3 ml) into the mouth by syringe will cause the animal to swallow, this may abate the bout of inspiratory dyspnea. Some owners feel stroking the neck or larynx will also help. The condition is ongoing and alarming to the owners but not life-threatening.

REFERENCES l. Barrett, R. E. , and Scott, D. W.: Treatment of feline cryptococcosis: Literature review and case report. J. Am. Anim. Hosp. Assoc., 11 :511-518, 1975. 2. Barrett, R. E., Hoffer, R. E., and Schultz, R. D. : Treatment and immunological evaluation of 3 cases of canine aspergillosis. J. Am. Anim. Hosp. Assoc., 13:328-334, 1977. 3. Bedford, P. G. C., Coulson, A., Sharp, N. J. H., et al.: Nasopharyngeal polyps in the cat. Vet. Rec., 109:551-553, 1981. 4. Bedford, P. G. C. : Origin of the nasopharyngeal polyp in the cat. Vet. Rec., 110:541-542, 1982. 5. Blue), L., and Nightingale, J. P. : Aspergillusfumigatus infection in the nasal cavity of a dog: Its treatment with amphotericin B. Vet. Rec., 92:447-450, 1973. 6. Bradley, P. A., and Harvey, C. E. : Intra-nasal tumors in the dog: An evaluation of prognosis. J. Small Anim. Pract., 14:459-467, 1973. 7. Bright, R. M. : Nasal aspergillosis in the dog. Compend. Contin. Ed. , 1:664-670, 1979. 8. Bright, R. M.: Nasal foreign bodies, tumors anci rhinitis/sinusitis. In Bojrab, M. J. (ed.): Pathophysiology in Small Animal Surgery. Philadelphia, Lea & Febiger, 1981, pp. 335-349. 9. Confer, A. W., and De Paouli, A.: Primary neoplasms of the nasal cavity, paranasal sinuses and nasopharynx in the dog. Vet. Pathol. , 15:18-30, 1978. 10. Davis, L. E.: Clinical pharmacology of the respiratory system. In Kirk, R. W. (ed.): Current Veterinary Therapy VII. Philadelphia, W. B. Saunders Co., 1980, pp. 208-213. 11. Ford, R. B.: Management of chronic upper airway disease. In Kirk, R. W. (ed.): Current Veterinary Therapy VIII. Philadelphia, W. B. Saunders Co., 1983, pp. 231-237. 12. Fraser, D. W., Ward, J. 1., Ajello, L., et al.: Aspergillosis and other systemic mycosis. · J. Am. Med. Assoc. , 245:1631-1635, 1979. 13. Gibbs, C., Lane, J. G. , and Denny, H. R.: Radiological features of intra-nasal lesions in the dog: A review of 100 cases. J. Small Anim . Pract., 20:515-535, 1979. 14. Goring, R. L., Ticer, J. W., Gross, T. L., et al.: Positive contrast rhinography: A technique for radiographic evaluation of the nasal cavity, nasopharynx and paranasal sinuses in the dog. Vet. Radiol., 25:99-105, 1984. 15. Goring, R. L., Ticer, J. W., Ackerman, N., et al.: Contrast rhinography in the radiographic evaluation of diseases affecting the nasal cavity, nasopharynx and paranasal sinuses in the dog. Vet. Radiol., 25:106-123, 1984.

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16. Harvey, C. E.: The nasal septum of the dog: Is it visible radiographically? Vet. Radiol., 20:88-90, 1979. 17. Harvey, C. E., Biery, D. N., Morello, J., et al.: Chronic nasal disease in the dog: Its radiographic diagnosis. Vet. Radiol., 20:91-98, 1979. 18. Harvey, C. E., O'Brien, J. A., Felsburg, P. J., et al.: Nasal penicilliosis in six dogs. J. Am. Vet. Med. Assoc., 178:1084-1087, 1981. 19. Harvey, C. E., and O'Brien, J. A.: Nasal aspergillosis-penicilliosis. In Kirk, R. W. (ed.): Current Veterinary Therapy VIII. Philadelphia, W. B. Saunders Co., 1983, pp. 236-241. 20. Harvey, C. E.: Surgery of the nasal cavity and sinuses. In Bojrab, M. J. (ed.): Current Techniques in Small Animal Surgery. Edition 2. Philadelphia, Lea & Febiger, 1983, pp. 253-257. 21. Harvey, C. E.: Nasal aspergillosis and penicilliosis in dogs: Results of treatment with thiabendazole. J. Am . Vet. Med. Assoc., 184:48-50, 1984. 22. Hayes, H. M., Wilson, G. P., and Fraumeni, J. F. : Carcinoma of the nasal cavity and paranasal sinuses in dogs: Descriptive epidemiology. Cornell Vet., 72:168-179, 1982. 23. Hermans, P. E ., and Keys, T. F. : Antifungal agents used for deep-seated mycotic infections. Mayo Clin. Proc., 58:223-231, 1983. 24. Lane, J. G., Clayton-Jones, D. G., Thoday, K. L., et al.: The diagnosis and successful treatment of Aspergillus fumigatus infection of the frontal sinuses and nasal chambers of the dog. J. Small Anim. Pract., 15:79-87, 1974. 25. Lane, J. G., and Warnock, D. W.: The diagnosis of Aspergillusfumigatus infection of the nasal chambers of the dog with particular reference to the value of the double diffusion test. J. Small Anim. Pract., 18:169-177, 1977. 26. Lane, J. G., Orr, C. M., Lucke, J., et al.: Nasopharyngeal polyps arising in the middle ear of the cat. J. Small Anim. Pract., 22:511-522, 1981. 27. Legendre, A. M., Spaulding, K., and Krahwinkel, D. J.: Feline nasal and paranasal sinus tumors. J. Am. Anim. Hosp. Assoc. , 17:1038-1039, 1981. 28. Legendre, A. M., Gompf, R., and Bone, D.: Treatment of feline cryptococcosis with ketoconazole. J. Am. Vet. Med. Assoc., 181:1541, 1982. 29. Legendre, A. M., Spaulding, K., and Krahwinkel, D. J.: Canine nasal and paranasal sinus tumors. J. Am. Anim. Hosp. Assoc., 19:115-123, 1983. 30. Moore, R.: Treatment offeline cryptococosis with 5-flucytosine. J. Am. Vet. Med. Assoc., 181:816-817, 1982. 31. MacEwen, E . G., Withrow, S. J., and Patnaik, A. K. : Nasal tumors in the dog: Retrospective evaluation of diagnosis, prognosis, and treatment. J. Am. Vet. Med. Assoc., 170:45-48, 1978. 32. Madewell, B. R., Priester, W. A., Gilette, E. L., et al.: Neoplasms of the nasal passages and paranasal sinuses in domestic animals as reported by 13 veterinary colleges. Am. J. Vet. Res., 37:851-856, 1976. 33. Medhoff, G., and Kobayashi, G.: Strategies in the treatment of systemic fungal infections. N. Engl. J. Med., 302:145-155, 1980. 34. Miller, M. E., Christensen, G. C., and Evans, H. E.: Anatomy of the Dog. Philadelphia, W. B. Saunders Co., 1979, pp. 158-159. 35. Morgan, J. P., Suter, P. F., and O'Brien, T. R.: Tumors in the nasal cavity of the dog: A radiographic study. J. Am. Vet. Radiol. Soc., 13:18-26, 1972. 36. Mullaney, T. P., Levin, S., and Indrieri, R. J. : Disseminated aspergillosis in a dog. J. Am. Vet. Med. Assoc., 182:516-518, 1983. 37. Norris, A. M.: Intranasal neoplasms in the dog. J. Am. Anim. Hosp. Assoc., 15:231-236, 1979. 38. Norris, A.M., Henderson, R., and Withrow, S. J.: Tumors of the respiratory system. In Slatter, D. H. (ed.): Textbook of Small Animal Surgery. Philadelphia, W. B. Saunders Co., In press. 39. O'Brien, J. A., and Harvey, C. E.: Diseases of the upper airway. In Ettinger, S. J. (ed.): Textbook of Veterinary Internal Medicine. Philadelphia, W. B. Saunders Co., 1983, pp. 692-722. 40. Palumbo, N. E., and Perri, S.: Amphotericin B therapy in two cases offeline cryptococcosis. Vet. Med. Small Anim. Clin., 70:553-557, 1975. 41. Parker, N. R., and Binnington, A. G.: Nasopharyngeal polyps in cats: Three case reports and a review of the literature. Submitted to the J. Am. Anim. Hosp. Assoc. 42. Poli, G., Ponti, W., Balsoni, A., et al.: Aspergillus fumigatus and specific precipitants in dogs with turbinate changes. Vet. Rec., 108:143-145, 1981.

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43. Priester, W . A., and McKay, F. W.: The occurrence of tumors in domestic animals. Natl. Cancer Inst. Monogr., 54, N.l.H. Publ. No. 80-2046. U.S. G. P.O., Washington, D .C., 1980. 44. Prevost, E., McKee, J. M., and Crawford, P. : Successful medical management of severe feline cryptococcosis. J. Am. Anim. Hosp. Assoc. , 18:111-114, 1982. 45. Pyle, R. L.: Clinical pharmacology of amphotericin B. J. Am . Vet. Med. Assoc. , 179:83-84, 1981. 46. Reif, J. S., and Cohen, D .: The environmental distribution of canine respiratory tract neoplasms. Arch. Environ . Health, 21 :136-140, 1971. 47. Richardson, R. C., Jaeger, L. A., and Wigle, W .: Treatment of systemic mycosis in dogs. J. Am. Vet. Med. Assoc., 183:335-336, 1983. 48. Roudebush, P.: Diagnostics for respiratory disease. In Kirk, R. W. (ed.): Current Veterinary Therapy VIII. Philadelphia, W. B. Saunders Co., 1983, pp. 222-230. 49. Soltys, M. A., and Sumner-Smith, G.: Systemic mycosis in dogs and cats. Can. Vet. J., 12:191-199, 1971. 50. Thrall, D. E., and Harvey, C. E.: Radiotherapy of malignant nasal tumors in 21 dogs. J. Am . Vet. Med. Assoc. , 183:663-666, 1983. 51. Weir, E. C., Schwartz, A., and Buergelt, C. D.: Short-term combination chemotherapy for treatment offeline cryptococcosis. J. Am. Vet. Med. Assoc., 174:507-510, 1979. 52. Wilkinson, G. T.: Feline cryptococcosis: A review and seven case reports . J. Small Anim. Pract., 20:749-768, 1979. 53. Wilkinson, G. T., Sutton, R. H., and Grono, L. R.: Aspergillus spp. infection associated with orbital cellulitis and sinusitis in a cat. J. Small Anim. Pract., 223:127-131, 1982. 54. Wilson, R. B.: Hypercalcemia associated with nasal adenocarcinoma in a dog. J. Am. Vet. Med. Assoc., 182:1246-1247, 1983. 55. Withrow, S. J.: Diagnostic and therapeutic nasal flush in small animals. J. Am. Anim. Hosp. Assoc., 13:704-707, 1977. 56. Withrow, S. J.: Cryosurgical therapy for nasal tumors in the dog. J. Am. Anim. Hosp. Assoc., 18:585-589, 1982. 57. Wood, G. L., Hirsh, D. C., Selcer, R. R. , et al.: Disseminated aspergillosis in a dog. J. Am . Vet. Med. Assoc., 172:704-707, 1978. The Veterinary Referral Clinic of Toronto 977 Eglington Avenue West Toronto, Ontario Canada M6C 2C4