Canine fungal rhinitis is a common disease that primarily affects young to middle-aged mesaticephalic (e.g., Labrador Retriever) and dolichocephalic (e.g., German Shepherd Dog) breeds. Aspergillus fumigatus, a ubiquitous soil saprophyte, is the most common pathogen, although Penicillium spp. and Cryptococcus neoformans have also been reported. Nasal aspergillosis is rare in cats. In one report of 60 dogs with nasal aspergillosis, the age of affected animals ranged from 3 months to 11 years (mean 3.3 years). In contrast, a major differential, nasal neoplasia, tends to occur in older animals. A history of nasal trauma is uncommon, but has been reported in some dogs. Nasal aspergillosis can occur concomitantly with, and probably secondary to, nasal tumours and nasal foreign bodies such as grass awns. Other differential diagnoses should include extension of dental disease, cleft palate, lymphoplasmacytic, bacterial and allergic rhinitis. It has been suggested that some dogs with nasal aspergillosis may have an underlying immunodeficiency that predisposes them to infection, and impaired lymphocyte blastogenesis responses have been reported. However, it is unclear whether impaired lymphocyte function is a cause or a result of infection, since A. fumigatus products have been shown to inhibit lymphocyte transformation in vitro.

Clinical and historical signs consistent with nasal aspergillosis in dogs include mucopurulent nasal discharge, sneezing, signs of nasal pain such as pawing at the face or pain on palpation, epistaxis, decreased appetite, lethargy and nasal depigmentation or ulceration. Stertor, stridor and/or open-mouth breathing may also be noted. Nasal discharge is initially unilateral in most cases, but often progresses to bilateral involvement. Facial deformity due to paranasal extension or inflammation can occur in advanced cases, and epiphora secondary to nasolacrimal duct obstruction occurs occasionally.

Diagnosis

A thorough physical examination should include facial palpation for evidence of pain or asymmetry, evaluation of airflow through each nostril, and an oral examination. Established guidelines used to make a definitive diagnosis, include positive results on biopsy, a positive titre with positive culture results, or a positive titre with radiographic or computed tomography (CT) scan changes suggestive of fungal rhinitis (turbinate loss). Unfortunately, confirmation of the diagnosis often requires multiple tests as Aspergillus fumigatus may be found as indigenous flora in the nasal cavity of many animals. Culture results may also be negatively impacted by secondary bacterial overgrowth.

Following radiographic or computed tomographic evaluation of the nasal cavity, rhinoscopy should be performed, preferably during the same anaesthetic episode. Nasal examination is never performed prior to radiography because haemorrhage induced by rhinoscopy will alter the results. General anaesthesia is required, with a cuffed endotracheal tube in place to prevent aspiration of blood and lavage fluids. The external surface of the nasal cavity is examined for evidence of swelling, asymmetry and ulceration. This includes a thorough oral examination, and visualisation of the nasopharynx with either a flexible fibreoptic scope or an angled dental mirror.

The advantages of direct visualisation of the nasal cavity include a more thorough understanding of the nature of the disease process, and the potential to place a biopsy instrument at the area of interest and to aid in the insertion of infusion catheters.

Biopsy specimens are placed in formalin for histopathological examination, in appropriate media for bacterial and fungal cultures, and rolled on to glass slides for immediate cytological examination. Following resolution of haemorrhage and prior to recovery from anaesthesia, the pharyngeal gauze sponges are recounted, and the pharynx is suctioned as needed.

Rhinoscopic evaluation of dogs with aspergillosis typically reveals areas of turbinate atrophy, mucopurulent discharge and fungal plaques. Fungal plaques may be white, off-white or have a greenish tint. Cytological evaluation of Aspergillus plaques reveals septate hyphae with dichotomous branching at 45 degree angles. Conidia may also be present.

If a diagnosis of nasal aspergillosis is confirmed following nasal examination based on consistent radiographic or CT findings, the presence of fungal plaques, and/or hyphae on cytological examination, then topical treatment may be performed during the same anaesthetic episode.

Treatment

Topical administration of the imidazoles, enilconazole and clotrimazole, is more effective than orally administered antifungal medications. Intranasal administration of enilconazole originally entailed a surgical procedure to place indwelling catheters into the nasal cavity, frontal sinuses, or both. After catheter placement, small volumes (5-10 ml (50 mg/ml = 10 mg/kg)) of enilconazole were administered twice daily for 7-14 days. Larger volumes were avoided because of risk of aspiration. In one study, nasal discharge resolved in 19 (80%) of 24 dogs treated solely with topical administration of enilconazole. Common complications included premature removal of catheters necessitating additional anaesthetic episodes for catheter replacement, transient postoperative subcutaneous emphysema, inappetence and ptyalism after administration of enilconazole.

A 1-hour infusion of clotrimazole or enilconazole, administered to dogs that are under general anaesthesia, also results in resolution of clinical signs in many dogs with nasal aspergillosis. Both drugs at the high local concentrations achieved with topical administration cause direct damage to fungal membranes, and inhibit fungal ergosterol synthesis.

One study evaluated 60 dogs with nasal aspergillosis treated with topical clotrimazole. Topical 1% clotrimazole solution was infused during a 1-hour period via surgically placed frontal sinus and nasal catheters (27 dogs) and via non-surgically placed intranasal catheters (18 dogs). An additional 15 dogs required and received two to four infusions by either route. Topical administration of clotrimazole resulted in resolution of clinical disease in 65% of dogs after one treatment and in 87% of dogs after one or more treatments. There was no difference in outcome between surgically and non-surgically placed catheters.

Non-Surgical Intranasal Placement of Infusion Catheters

General anaesthesia is induced and the dog is intubated with a cuffed endotracheal tube. Catheters are placed with the dog in lateral recumbency. A 24 Fr Foley catheter is placed through the mouth so that the tip of the catheter is dorsal to the soft palate. This process is aided initially by grasping the catheter tip with a pair of long-handled needle holders so that the catheter tip is directed rostrally. A mouth gag is placed and an assistant pulls the dog's tongue rostrally to improve exposure. The Foley catheter is advanced until its balloon is dorsal to the junction of the hard and soft palates. The balloon is inflated to occlude the nasopharynx, and is palpated through the soft palate to confirm its position. Precounted laparotomy sponges are placed in the pharynx so that the catheter cannot migrate caudally, and to absorb any infusate that might escape around the balloon. Smaller sponges are avoided as these are easily swallowed. The index finger of the operator's opposite hand is used to maintain balloon position during sponge placement. The mouth gag is removed. One 10 Fr polypropylene infusion catheter is advanced, beginning dorsomedially, through each nostril into the dorsal nasal meatus, to the level of the medial canthus of the ipsilateral palpebral fissure. A 12 Fr Foley catheter is inserted into each nostril and the balloons are inflated so that they are positioned just caudal to and occluding the nostrils. A nylon suture is placed across each nostril to prevent rostral migration of the balloons. The balloons of the three Foley catheters (i.e., one nasopharyngeal, two nasal) serve to slow leakage of clotrimazole.

The dog is then placed in dorsal recumbency, and an additional laparotomy sponge position just caudal to the upper incisors between the endotracheal tube and the incisive papilla to control leakage of clotrimazole through the incisive ducts. A 1% clotrimazole solution (Lotrimin® solution, Schering Corporation) is evenly divided between two 60 ml syringes and slowly infused during 1 hour. The polypropylene catheters are maintained parallel to the table throughout the infusion. The Foley catheters theoretically allow air to escape from the nasal chamber during the infusion. When fluid is noticed within the lumen of a Foley catheter it is clamped. The dog is positioned so that its nose protrudes beyond the edge of the treatment table. The dog's head is rotated and maintained in the following positions to ensure drug contact with all nasal surfaces: dorsal recumbency (15 minutes), left lateral recumbency (15 minutes), right lateral recumbency (15 minutes), ventral recumbency (15 minutes). Following treatment, the nasal catheters are removed and the nasal cavity allowed to drain prior to removing and counting pharyngeal sponges and the pharyngeal catheter.

The volume of the nasal cavity and frontal sinuses varies depending on the size of the dog, the extent of turbinate destruction, and the volume of accumulated exudate. Based on a study in cadavers, the average volume of the frontal sinuses in breeds predisposed to fungal rhinitis was 25 ml per side. The nasal cavity and sinuses can be flooded with a larger volume of infusate (50-60 ml per side), resulting in distribution of the infusate to all areas of the nasal cavity and frontal sinuses. A 1% formulation of clotrimazole in a polyethylene glycol base is readily available in a 30 ml vial, which makes treatment with two vials per side convenient. 60 ml per side is used in medium to large-breed dogs regardless of head size. 30 ml per side should be adequate for smaller breeds. Formulations that contain isopropyl alcohol and propylene glycol (Canesten® Solution) should be used with caution as they may result in pharyngeal irritation and oedema.

After Care

Complications in dogs treated with intranasal infusion of clotrimazole are generally limited to leakage of clotrimazole through the incisive ducts during treatment, which is easily controlled with digital pressure, and transient increases in nasal drainage or sneezing immediately following recovery from anaesthesia. Nasal discharge ceases in most dogs by 2 weeks after topical clotrimazole therapy. A repeat treatment is recommended if nasal discharge continues without improvement 2 weeks after the initial treatment. Owners of affected dogs with high CT scores should also be advised that more than one treatment would probably be needed. Sequential evaluation of Aspergillus titres does not aid in the decision to retreat as titres may remain elevated for years despite resolution of disease. Recurrent nasal discharge that resolved with empirical antibiotic therapy occurred in 7/60 dogs (a mean of 4 months following antifungal treatment). Secondary bacterial rhinitis was suspected in these dogs, possibly because of destruction of the nasal anatomy by the fungal infection. Once nasal discharge ceases after clotrimazole treatment, it appears that a recurrence of rhinitis attributable to fungal infection is uncommon and was documented in only one of 60 dogs.

Topical administration of clotrimazole, using either technique, is therefore an effective treatment for nasal aspergillosis in dogs. The use of non-invasive intranasal infusion of clotrimazole eliminates the need for surgical trephination of the frontal sinuses in many dogs and is associated with fewer complications. Having said this, dogs with bulky disease (usually seen as a fungal granuloma within a sinus on CT) respond better if the granuloma is removed prior to treatment. This usually requires a limited sinusotomy. Following debulking, a catheter can be placed in the contralateral sinus for infusion of clotrimazole, while the surgically treated sinus is simply filled with drug and 'topped off' as needed during the 1 hour treatment.

Summary

 CT imaging is preferred over radiographs to define extent of disease and in particular to determine if there is cribriform plate involvement or if there are fungal granulomas

 Oral antifungal therapy is generally only used if cribriform plate erosion eliminates the possibility of treating the dog topically

 Topical therapy can be performed non-invasively if there is no bulky disease

 The presence of a fungal granuloma requires debridement either endoscopically or via a limited sinusotomy prior to topical therapy

What's On the Horizon?

Increasing the viscosity of topical antifungal drugs used to treat this condition could result in decreased anaesthesia time, and most importantly could prolong drug contact with residual fungus and increase the likelihood of a successful outcome. Filling the frontal sinuses with the commercially available clotrimazole cream has been preliminarily evaluated in 14 dogs with fungal rhinitis. Results were good in 12/14 cases. The severity of disease in these cases was unclear, and the length of time the drug was retained in the sinuses was not evaluated. Questions that remain regarding depot therapy include:

 What is the ideal drug formulation that will maximise success while limiting inflammatory response to the drug/vehicle?

 How much contact time is ideal?

 Is prolonged contact time associated with side effects due to drug absorption?

A pilot study, which investigated the retention time, and inflammatory response to different 1% clotrimazole formulations, will be covered in our discussion.

References

1.  Harvey CE. Nasal aspergillosis and penicilliosis in dogs: results of treatment with thiabendazole. Journal of the American Veterinary Medical Association 1984; 184: 48-50.

2.  Sharp NJH, Sullivan M. Use of ketoconazole in the treatment of canine nasal aspergillosis. Journal of the American Veterinary Medical Association 1989; 194: 782-786.

3.  Sharp NJH, Harvey CE, O'Brien JA. Treatment of canine nasal aspergillosis/penicilliosis with fluconazole (UK-49,858). Journal of Small Animal Practice 1991; 32: 513-516.

4.  Sharp NJH, Harvey CE, Sullivan M. Canine nasal aspergillosis and penicilliosis. Compendium on Continuing Education 1991; 13: 41-49.

5.  Sharp NJH, Sullivan M, Harvey CE. Treatment of canine nasal aspergillosis. In Practice 1992; 14: 27-31.