Canine fungal rhinitis
In the UK, the primary cause of fungal rhinitis is Aspergillus fumigatus. In other parts of the world different fungi have been identified including other strains of Aspergillus, Penicillium and Scedosporium. The underlying pathology is of a destructive rhinitis. A fumigatus is ubiquitous in the environment, although the heaviest concentrations are in specific situations such as damp or badly stored hay/straw or composting grass clippings. It is still unclear why some dogs appear to develop an active infection with the development of large numbers of hyphae and fungal colonies, whilst the majority of dogs simply harbor some spores as normal inhalants.
Certainly some predisposing factors have been implicated in a small proportion of cases, such as trauma, septicemia, or other intercurrent disease (including nasal neoplasia). Severe immunocompromise, one of the main factors for human aspergillosis in the Western world, has not been substantiated in the dog, or indeed the cat. The evidence of impaired cellular immunity in canine aspergillosis may be due to the effect of the fungus rather than pre-existing in the animal.
The first description of this condition dates from 1905, and aspergillosis is now well recognized as a cause of chronic nasal discharge in the dog. However, it does require to be differentiated from a number of other conditions before satisfactory management can be instigated. On the basis of rhinoscopic and diagnostic imaging findings, the infection is well established by the time of diagnosis in the majority of cases. This is probably due to the fact that the nasal discharge – the major presenting sign – has been either licked from the external nares or drawn caudally to thenasopharynx and swallowed for some time before the animal is presented to the veterinarian.
Key differential diagnoses
• Fungal rhinitis
• Chronic rhinitis
• Foreign body
• Dental disease
The less common causes are perhaps only considered if there is direct evidence in the consulting room (e.g. detection of a cleft palate) or after the above key differentials have been ruled out. A preliminary sifting of the various possibilities may be done on the basis of history. However, it would be fair to say that it is easy for a clinician to be wrong-footed by a manifestation that has not followed the classic descriptions.
As might be expected, the main reason for the owner presenting the animal is nasal discharge. Unfortunately, the type of discharge and whether it is unilateral or bilateral is unhelpful. This is because the discharge may vary from serous inthe early stages to mucopurulent ± blood to even frank epistaxis. These discharges, individually, can be seen in any of the above conditions. Laterality is also too non-specific. Age is often quoted as a differentiating factor, but there is too much overlap for this to be used to rule in or rule out particular conditions. Targeted questions may elicit manifestations of facial pain, which is a specific pointer.
In advanced cases, the animal may present as having fits, or even collapse of the nasal bones. The owner may report non-nasal signs of reduced appetite and dullness.
At the time of presentation many animals are not exhibiting nasal discharge, but evidence of facial pain can be detected by moving one’s hand towards the nose or gently tapping the nasal and frontal bones. A key and pathognomonic feature is the presence of ulceration and depigmentation of the external nares, particularly the nasal sill (Figure 1). Hyperkeratosis may also be present. A normal airflow will be found, which helps distinguish it from nasal neoplasia where airflow is usually impaired.
In summary aspergillosis may be strongly suggested on the basis of:
• Facial pain
• External naral depigmentation/ulceration
• Normal airflow
At the time of the consult where aspergillosis is suspected, the most appropriate next step is to obtain a serum sample for submission to a reference laboratory to have serology antibodies detected. Having the result expressed in terms of titers is quite helpful. Admittedly there can be some false negatives and positives, but false positives tend to have a faint response and so are reported as a trace. If the titer is returned positive then one can proceed with further investigative tests to verify diagnosis and thus establish management options with more confidence. The next stage requires general anesthetic.
Whilst computed tomography (CT) may be claimed by some to be the most valuable diagnostic imaging modality, others would no doubt make the same claim for magnetic resonance imaging (MRI). However few practices have either of these options and nasal aspergillosis does not need referral to specialist centers for diagnosis and treatment.
The diagnostic imaging features are similar on all modalities, where destruction of the turbinates is evident leading to an empty space or void seen as a radiolucent, hypoattenuating (CT) or signal void (MRI). Depending on the degree of involvement the changes are initially seen in the ventral concha or in the rostral portion of the nasal cavity. Caudally, in the ethmoturbinate area a mixed appearance is evident on radiographs, which is due to a combination of truncated turbinates, swollen mucosa, discharge and fungal plaques. In extreme cases, actual granulomas or fungal balls may be present (Figure 2).
Historically, non-screen film for the dorso-ventral intra-oral (DVIO) view gave the best image for radiography, but this type of film has either been withdrawn or will no longer be adequately developed by modern automatic processors. Extraction of intensifying screens and placing these along with film in a flexible light-proof plastic envelope still allows this view to be obtained, albeit with distinct shortening of the life of the screens and less sharpness than with non-screen film. As technology has advanced the introduction of digital systems (either direct or computed) has increased the use of the alternative intra-oral view, the ventro-20°-dorsal intra-oral. Whilst a DVIO is possible if the reader plate is removed from a CR cassette and then put back into the cassette after exposure, the cost of these plates makes this method a luxury. To assess the frontal sinuses requires a second view, either rostro-caudal, or caudo-rostral if the equipment and controlled area permit a horizontal beam.
CT, where available, has the distinct advantage (as with all cross-sectional imaging modalities) of avoiding superimposition. The features are the same as with conventional radiographs, though with more clarity, where destruction of turbinates and hypoattentuation predominates. Further advantages of CT are that the same study will permit evaluation of the frontal sinuses, and the nasal septum can be better visualized (Figure 3) (Weblink 1).
Under general anesthetic for diagnostic imaging, the nasal cavity may be examined. What endoscope is used depends on availability; auroscope, arthroscope, flexible endoscope or dedicated rhinoscope. Regardless of the instrument used, the features to look for are a lack of turbinates and the presence of dryish fungal plaques; mucopus will glisten (Figure 4). If plaques are seen they may be sampled to derive a better and substantial growth compared to the typical sparse growth gained from blind swabs (Weblink 2).
Over the years a plethora of treatments have been tried. This fact alone indicates that the fungus has proved resistant to clearance in all animals treated. Of course this begs the question; is it the animal’s lack of immune response which allows persistence/reinfection or is the fungus resistant? It is well known that fungal infections are difficult to treat and that systemically the therapeutic index is not as wide as is typical of most drugs. Early treatments were combined with turbinectomy and curettage, the latter subsequently being shown to have an adverse effect on cure rates. Later treatments focusing on oral delivery have not been sustained because of poor absorption from the alimentary tract and difficulty in establishing minimal inhibitory concentrations in the nasal mucosa. The efficacy of the drug in the nasal mucosa is hampered by the fact that the bulk of the fungus has neither invaded the mucosa or is in contact with the mucosa (as the rhinoscopic figures illustrate). Thus in the last 20 years the center of attention has been on topical delivery. The factors that have been investigated are the drug, access for delivery and treatment times.
Perhaps the first “modern” treatment was the use of enilconazole delivered through drains implanted in the frontal sinuses. A tube was inserted to the level of the carnassial tooth, with a second, shorter one terminating in the frontal sinus if it was involved. The dose was rather empirical (10 mg/kg diluted with water to 5 mL per tube twice daily). The drug was flushed through the tubes ensuring that the animal’s head was pointed vertically towards the floor. This was to minimize run-off into the pharynx and ingestion of the drug. Air was then flushed through the drains to clear any retained drug. This treatment required hospitalization because of the twice-daily delivery and the need for restraint as the dog often began to resent the drug flushing due to significant discomfort. However, this treatment appeared to give rise to a success rate after one treatment of >90%, but clearly this method had a number of disadvantages, namely hospitalization, manpower and - most importantly - animal pain.
In general the results with enilconazole were disappointing, and an alternative method was proposed and has become accepted as the first line of treatment. The concept was predicated still on delivery of a drug topically but over a shorter and more intense period. The drug chosen this time was clotrimazole 1% solution. The animal is anesthetized and the external nares and caudal chonae are occluded. The best method of drug infusion is still debatable. One school of thought holds that introduction of clotrimazole through the external nares is satisfactory regardless of frontal sinus involvement. However, an alternative view is that if there is frontal sinus involvement the ostia may be narrowed due to inflammation, and the filling of the sinuses by fungus may inhibit drug access. Consequently, inserting drains into the frontal sinus was viewed as a more confident method of ensuring contact between drug and fungus in the frontal sinus. Initial reports involved use of clotrimazole solution. Latterly, clotrimazole cream has been pumped into the frontal sinuses and nasal cavity, the theory being that the cream will remain in the nasal cavity for longer than the solution.
Using the solution through external naral tubes or frontal sinus ports, it has proved difficult to avoid leakage. Occlusion of the external nares can be done with Foley catheters. However, placing these catheters in the nasopharynx so that, when inflated, they do not retract caudally is difficult to achieve if the oropharynx is not plugged with dampened swabs, trapping the catheter with the soft palate. Indeed nasopharyngeal leakage is very likely, to the extent that it has been suggested that using an assistant’s hand to maintain the soft palate against the dorsal pharyngeal wall facilitates occlusion.
Under general anesthetic the clotrimazole solution is flushed into the nasal cavity (Figure 5). Every 15 minutes the animal is rotated 90° to ensure adequate contact, so that after one hour the animal has been rotated 360°. Note that the drug needs to be topped up during the contact time, thus perhaps 2x60 mL bottles will be required. At least one study has monitored the amount of drug required by measuring intra-nasal pressure during treatment. Published success is about 80% after one treatment.
The only reliable method is rhinoscopy one month after treatment. Certainly continued (or resumption of) purulent discharge is suggestive of fungal presence. However, given the turbinate damage, some animals that have persistent discharge (though at a low level) may actually have a secondary bacterial rhinitis, which will resolve on broad-spectrum antibiosis. If at follow-up there is still fungus present then a second treatment is justified. However, if a third treatment is required then it might be argued that a return to enilconazole flushing is indicated, or adding ketoconazole (40 mg/kg for 6 weeks) as an oral supplement. Using ketoconazole requires that liver enzymes be monitored for evidence of hepatic damage. In addition, some animals develop vomiting and diarrhea on ketoconazole that requires cessation of the drug for a 5 day hiatus then gradual reinstatement of the oral treatment.
The prognosis does depend on how invasive the fungus has been. Sole involvement of the cavity carries the best prognosis, whereas invasion of the frontal bones and breaching of the cribriform plate are increasing negative factors. Owners need to appreciate that whatever treatment is used, success cannot be guaranteed with one treatment. To date there have been a reasonable number of publications relating successful treatment or otherwise. However, too few studies have followed the same protocol and thus the numbers reported in each study are relatively small.
Canine nasal fungal infections are widespread throughout the world and can cause severe tissue destruction. Diagnosis can be done without referral to specialist centers and successful treatment can be achieved but is by no means guaranteed in every case. However the clinician is reminded that failure to recognize the infection can lead to death.
FURTHER READING AND MEDIA LINKS
• Burbidge HM, Clark WT, Read R, et al. Canine nasal aspergillosis: results of treatment using clotrimazole as a topical agent. Austr Vet Pract 1997; 27: 79-83.
• Hector R, Kass P. Comparison of topical administration of clotrimazole through surgically placed versus non-surgically placed catheters for treatment of nasal aspergillosis in dogs: 60 cases (1990-1996). J Am Vet Med Assoc 1998; 213: 501-506.
• Mathews K, Davidson A, Koblik P, et al. Update on canine sinonasal aspergillosis. Vet Clin North Am – Small Anim Pract 2007; 37: 901-916.
• Peeters D, Day MJ, Clercx C. An immunohistochemical study of canine nasal aspergillosis. J Comp Path 2005; 132: 283-288.
• Schuller S, Clercx C. Long-term outcomes in dogs with sinonasal aspergillosis treated with intranasal infusions of enilconazole. J Am Anim Hosp Assoc 2007; 43: 33-38.
• Sharp N, Sullivan M, Harvey C, et al. Treatment of canine nasal aspergillosis with enilconazole. J Vet Inter Med 1993; 7: 40-43.
• Sissener TR, Bacon NJ, Friend E, et al. Combined clotrimazole irrigation and depot therapy for canine nasal aspergillosis. J Small Anim Pract 2006; 47: 312-315.
• Weblink 1: http://commsvs1.cent.gla.ac.uk/Vetmed_secure/MS/CTAspergillosis.wmv
• Weblink 2: http://commsvs1.cent.gla.ac.uk/Vetmed_secure/MS/Aspergillosis.wmv
This article was previously published in 2012.