Chronic nasal discharge and sneezing are common clinical complaints in dogs. The most common causes include neoplasia, aspergillosis, nasal foreign body, rhinitis secondary to dental disease, and idiopathic or inflammatory rhinitis. An accurate history, physical examination, and a complete diagnostic work-up are helpful in determining the etiology of disease; however, these disorders are challenging to control and are often refractory to therapy.
Nasal tumors represent a small percentage of neoplasms in animals; however, the majority of cases exhibit malignant behavior through local invasion of facial bones or the central nervous system and via extension to regional lymph nodes. Tumor types include lymphosarcoma, adenocarcinoma, squamous cell carcinoma, undifferentiated carcinoma, and fibrosarcoma.
Nasal aspergillosis is most commonly seen in young to middle-aged dolicocephalic dogs. German shepherd dogs and Rottweilers seem to be predisposed. In some (likely rare) cases, Aspergillus invasion occurs because of previous trauma to the nose or in association with a nasal foreign body.
Idiopathic lymphoplasmacytic rhinitis (LPR) has been referred to as immune-mediated or allergic rhinitis because initial reports of this disorder suggested that steroid therapy was curative; however, more recent evidence suggests these dogs often fail to respond to steroid therapy. It is critical to rule out all possible causes of nasal discharge before assigning a diagnosis of LPR because it has a poor prognosis for control. Dogs with idiopathic LPR, generally, are young to middle-aged, large breed dogs. Males and females are equally affected. German shepherd dogs and shepherd mixes, Labrador retriever mixes, and Collies are affected commonly.
Clinical Signs
Dogs with nasal neoplasia develop typical clinical signs of nasal discharge (usually unilateral initially, but may become bilateral), epistaxis, sneezing, and pawing at the face. Neurologic signs, such as seizures, behavioral changes, or cerebral dysfunction, can be seen alone or in conjunction with nasal discharge. The presence of these signs is highly suggestive of tumor invasion into the central nervous system and warrants a guarded prognosis. Dogs with nasal aspergillosis usually present with copious nasal discharge that is usually unilateral initially but may become bilateral, and depigmentation of the nasal planum may be noted by the owner. Chronic unilateral or bilateral nasal discharge is the most common clinical complaint in dogs with LPR. Discharge is typically mucoid or mucopurulent in most dogs and hemorrhagic or blood tinged discharge is not uncommon.
Physical Exam
Physical examination should include an assessment of nasal airflow (decreased or normal, unilateral or bilateral change), because loss of nasal airflow is a common finding in a neoplastic process, whereas it is typically preserved in aspergillosis. Palpation of the palate and facial bones for pain, swelling, or evidence of bony lysis may indicate that aspergillosis or neoplasia is more likely as a diagnosis. Dental examination and palpation of the gingival margins will help rule out periodontal disease as a cause for epistaxis or nasal discharge; however, occult dental disease or oronasal fistulae can be easily missed on physical exam. Neurologic exam should focus on detecting signs of cerebral dysfunction such as weakness and visual deficits. These may signify either neoplastic invasion of the cranium or extension of a fungal infection through the cribriform plate.
Diagnostic Testing
A minimum database is required for animals with nasal discharge since further diagnostics will require general anesthesia. A platelet count and coagulation profile should be obtained when hemorrhagic nasal discharge is present, and blood pressure evaluation should be performed when epistaxis is the primary complaint. A buccal mucosal bleeding time might also be considered if platelet or vascular function may be compromised. Whenever possible, regional lymph nodes should be aspirated, as this is the most common site for neoplastic spread. When suspicious of aspergillosis, fungal serology (agar gel immunodiffusion) should be considered since a positive result is likely to indicate disease, although a negative test does not rule it out.
The second wave of diagnostics includes skull radiographs or CT under general anesthesia and rhinoscopy with biopsy. A full skull series would include lateral views, an open mouth or intra-oral view, and the frog-eye view that highlights the frontal sinuses. Visualization of nasal structures is limited on the lateral view because of superimposition of densities in the region of the nasal cavity, but it may show loss of the air column within the nasopharynx, suggesting the presence of a mass lesion. The most useful view is the open-mouth view since it allows characterization of bony destruction and turbinate lysis within each side of the nasal cavity. Radiographic changes seen in nasal neoplasia include increased soft tissue density in the nasal cavity, lysis of the nasal turbinates, and lysis or deviation of the vomer bone. However, nasal radiography has low sensitivity in differentiating inflammatory rhinitis from neoplasia or mycotic rhinitis, since soft tissue opacification, turbinate destruction, and frontal sinus disease can be seen with all three conditions.
It is unquestionable that computed tomography provides more complete information on the nature and extent of disease within the nasal cavity. Tumors lead to turbinate destruction that can involve one or both nasal cavities, soft tissue masses that are either unilateral or bilateral, and sinus disease due to mass effect or obstruction of fluid drainage. Importantly, CT allows evaluation of the cribriform plate. Tumor-related destruction of this bony barrier to the central nervous system warrants a guarded prognosis. Finally, CT scans are recommended in the staging of nasal tumors in order to define tumor boundaries and to plan radiation therapy.
Diagnosis of aspergillosis is made by a combination of characteristic findings on CT and rhinoscopy, as well as detection of fungal hyphae in biopsy samples of plaques from the nasal cavity. CT usually reveals dramatic turbinate loss in the nasal cavity, with variable sinus involvement. In some cases, only the sinuses are involved and fungal granulomas can be visualized in this region with various imaging modalities. CT is preferred for evaluation of dogs with Aspergillus because it provides the opportunity to evaluate the integrity of the cribriform plate prior to local anti-fungal therapy.
The diagnostic work-up for LPR serves to rule out aggressive causes of nasal discharge, such as neoplasia or aspergillosis that require specific treatment. Computed tomography provides improved definition of the extent and severity of abnormalities of the nasal cavity, although LPR can cause aggressive CT lesions that mimic those found with these other conditions. Turbinate destruction is found commonly, although it is generally mild or moderate in most cases. Fluid accumulation, soft tissue opacification, gas pocketing, and frontal sinus involvement are also common CT findings, and abnormalities can be unilateral or bilateral.
Rhinoscopy should follow any imaging procedure. Caudal rhinoscopic assessment of the choanae is performed first, with biopsies as indicated. Following this, a moistened lap pad is packed around the endotracheal tube to prevent aspiration of fluid, blood, or tissue during rostral rhinoscopy. Biopsies of masses or fungal plaques should be obtained with direct visualization with rhinoscopy whenever possible. Saline flush and suction can improve visualization when mucus or blood obscures the view. When sampling within the nasal cavity, the biopsy instrument should not be extended beyond the medial canthus of the eye in order to avoid penetrating the central nervous system. When nasal neoplasia is suspected, collection of multiple biopsy samples is recommended to increase the likelihood of obtaining a diagnosis; however, bleeding can be significant. Use of hydropropulsion can clear the nasal cavity of bleeding and can enhance release of tissue fragments from the tumor, which can be collected from a lap pad packed around the endotracheal tube. Cytologic impression smears of mass lesions or apparent fungal plaques cytology can be used to get an early idea of the diagnosis, although histopathology is generally required to document neoplasia.
As mentioned, rhinoscopy is an important part of both diagnosis and therapy for aspergillosis. Visualization of fungal plaques with biopsy of these lesions provides the diagnosis. It is important to biopsy the plaque itself, since surrounding nasal tissue may be characterized by lymphoplasmacytic or neutrophilic rhinitis. The fungi are observed as long, septate hyphae.
In LPR, rhinoscopy typically reveals hyperemic, friable, inflamed epithelium, and mucus accumulation. Mild turbinate destruction is sometimes seen. Biopsies reveal variable severity of lymphoplasmacytic infiltrates, mucosal edema, and bony remodeling of turbinates. Culture of nasal swabs usually results in minimal growth of bacterial flora and does not contribute substantially to management of disease. Molecular studies suggest an increase in fungal DNA in the nasal cavity of dogs with LPR; however, it is unclear what role this might play in disease or therapy.
Treatment
Nasal lymphoma (more common in cats than in dogs) typically responds to radiation therapy or chemotherapy. Other tumors respond variably to radiation therapy, with predicted disease-free intervals ranging from 6–16 months depending on the size of the tumor and local spread. Predictable early side effects of radiation therapy include mucositis and skin irritation. When radiation therapy is not an option, chemotherapy might be considered. Some success has been reported using combination therapies. Finally, piroxicam (0.3 mg/kg PO once daily) is recommended for palliative therapy of epithelial or mesenchymal nasal neoplasia until epistaxis or neurologic signs worsen quality of life. Chemoembolization is a new, minimally invasive technique that is being performed on dogs that are not candidates for radiation therapy.
Nasal infection with Aspergillus is best treated with topical infusion of an anti-fungal agent (clotrimazole or enilconazole) since oral agents have relatively poor efficacy against infection. Clotrimazole has been reported to be effective as a single, one-hour instillation, with 39 of 60 dogs cured in one study. A second treatment cured an additional 11 of 60 dogs. Clotrimazole is available over the counter as a 1% solution in 10-ml bottles. One hour infusion of enilconazole given for 2–3 treatments through endoscopically placed tubes has also been effective in the cases reported. Enilconazole is supplied as a concentrated, commercial-grade solution that must be diluted to a 1, 2, or 5% solution prior to instillation in the nasal cavity.
If local therapy for Aspergillus is not possible because the cribriform plate is breached or neurologic signs are evident, the best option for therapy would likely be voriconazole, a new generation azole used in human medicine. However, this medication is very expensive and has not been evaluated in veterinary medicine. Itraconazole therapy is preferred over ketoconazole because of greater efficacy and fewer side effects. Itraconazole, administered at 5 mg/kg BID for 2–6 months may cure up to 60% of dogs with aspergillosis, although some studies have shown no effect of itraconazole on nasal aspergillosis.
Treatment of dogs with idiopathic LPR is frustrating. Systemic and topical corticosteroids do not appear to be effective in controlling signs in most dogs, and attempts at allergen avoidance may or may not be helpful. Modulatory anti-microbial therapy with long-term doxycycline or azithromycin, and anti-inflammatory treatment with piroxicam can be helpful in some dogs, although a guarded prognosis for cure must be given. Further investigations into the potential etiology of lymphoplasmacytic infiltration of the nasal cavity are required for improved treatment recommendations.
References
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