Aspergillosis in dogs is caused by *Aspergillus* species, saprophytic and ubiquitous filamentous fungi involved in environmental recycling that may also act as opportunistic pathogens. Their small size (2-3 microns) enables them to remain airborne and penetrate the respiratory tract. Most humans inhale several hundred conidia daily. The respiratory defence system (mucociliary escalator, cell-mediated immunity, and soluble mediators) eliminates these pathogens, preventing colonization within the respiratory system. However, changes in any component of the defence system may lead to the development of infection. In dogs, two forms of aspergillosis in dogs are reported: sinonasal aspergillosis (SNA), where the infection is restricted to the nasal cavities and frontal sinuses, and systemic aspergillosis, where the infection spreads deeper into the body.
Causes of Aspergillosis in Dogs
Fungal rhinosinusitis is one of the most common causes of chronic nasal discharge in dogs. The disease is primarily caused by Aspergillus fumigatus, though Aspergillus niger, Aspergillus nidulans, Aspergillus flavus, Aspergillus tubingensis, Aspergillus uvarum, and species of Penicillium have also been occasionally documented. On rare occasions, other mycotic agents such as Cryptococcus neoformans or Scedosporium apiospermum may affect the nasal cavities of dogs.
Pathogenesis of Aspergillosis
The pathogenesis of Aspergillus fumigatus in causing aspergillosis in dogs remains unclear, as only a small proportion of exposed dogs develop the disease. In rare cases, predisposing factors such as nasal foreign bodies, facial trauma, nasal tumours, or impacted teeth are present. Typically, affected dogs are not systemically immunocompromised, and fungal infections remain restricted to the nose and/or frontal sinuses without fungal invasion of respiratory mucosa. This suggests local nasal mucosal immune dysfunction may play a role in aspergillosis in dogs. There seems to be an imbalance between pro-inflammatory (Th1) and anti-inflammatory (Th17 and possibly T regulatory cells) signals, which could perpetuate the infection and its inflammatory response. A defect in Toll-like receptor (TLR) expression or function might be the primary dysfunction leading to the infection in dogs.
Sinonasal aspergillosis (SNA) is characterized by severe nasal turbinate destruction, likely caused by the inflammatory response and fungal toxins. In severe cases, bony destruction can occur, allowing inflammation to spread into peri-sinusal and periorbital soft tissues, and potentially into the brain.
Clinical Signs of Aspergillosis in Dogs
Signs of aspergillosis in dogs, particularly sinonasal aspergillosis (SNA), primarily affect young to middle-aged dogs of large mesaticephalic and dolichocephalic breeds. Common symptoms include sneezing, reverse sneezing, unilateral epistaxis (which may become bilateral as the disease progresses), and muco- or sanguinopurulent nasal discharge that can persist for weeks to months before examination. Other signs of aspergillosis in dogs include nasal planum depigmentation and ulceration, normal or increased ipsilateral nasal airflow, facial discomfort, lethargy, and decreased appetite, which are not typically seen with other causes of nasal discharge. In rare cases, inflammation can extend into the forebrain due to cribriform plate destruction, potentially leading to dullness or seizures.
Diagnosis of Aspergillosis in Dogs
Even when SNA is highly suspected based on signalment and a typical clinical presentation, fungal infection must be confirmed prior to therapy. No test is 100% accurate and a combination of diagnostic procedures is required. These include observation of destructive, “cavitating” changes of the nasal cavity by diagnostic imaging or rhinoscopy, and the demonstration of a fungal aetiology with endoscopic visualization of fungal plaques, cytology, histology, fungal culture and/or serology.
Imaging
Diagnostic imaging studies should be performed prior to rhinoscopy because resultant hemorrhage may obscure subtle lesions and induce imaging abnormalities. Several studies have demonstrated the higher sensitivity of computed tomography (CT) and magnetic resonance imaging (MRI), as compared to radiography, for the diagnosis of sinonasal diseases in dogs. CT is particularly superior to radiography for defining the extent of the sinonasal lesions, detecting cortical bone lesions and in assessing integrity of the cribriform plate.
The latter may be essential when choosing a therapeutic plan. The typical CT findings in sinonasal aspergillosis include: (1) moderate to severe cavitary destruction of the turbinates, often accompanied by varying amounts of abnormal soft tissue, such as secretions or fungal material, within the sinus or nasal cavities; (2) non-specific mucosal thickening adjacent to the inner surfaces of the bones in the frontal sinus, maxillary recess, and nasal cavity; and (3) thickened reactive bone formation. There is no clear advantage of using MRI versus CT in the diagnosis of canine sinonasal aspergillosis.
Endoscopy
Endoscopic examination of the sinonasal cavities is the only procedure that may allow diagnosis (fungal plaques visualization and/or target sampling) and treatment (debridement ± foreign body retrieval, and infusion catheters placement) of the infection during one general anesthetic. Typical rhinoscopic findings include moderate to severe destruction of the turbinates, resulting in a typical cavity-like appearance, roughening of the mucosa, presence of intranasal (sanguino-) mucopurulent secretions and fungal colonies.
In certain instances, damage to the nasal septum and the presence of disease on both sides may be noted. Fungal colonies typically appear as white or greenish fuzzy plaques adherent to the nasal or sinusal mucosa. In some cases, fungal colonies may not be present in the nasal cavities, and frontal sinus access is required for the diagnosis of sinonasal aspergillosis. In one study, sinus trephination with sinuscopy was necessary to confirm the diagnosis of sinonasal aspergillosis in 17% of dogs with CT lesions suggestive of the disease.
Rhinoscopy is usually performed with a 0° or 30° viewing angle rigid endoscope, but a flexible small endoscope should be used whenever possible to facilitate entry into the frontal sinus in some dogs. This is generally feasible in medium- to large-breed dogs with moderate to severe turbinate destruction. The major limitations of endoscopy are its inability to evaluate bony structures and, especially, the integrity of the cribriform plate. For this reason, endoscopy and CT are considered complementary diagnostic procedures.
Cytology
Cytology may be used to confirm the diagnosis of SNA. The sensitivity of this technique depends on the sampling method. Direct smears from nasal exudate and blind endonasal swabs detected fungal hyphae in only 13% and 20% of the cases, respectively, while brushing of suspected lesions under endoscopic guidance and squash preparation of biopsies of suspected lesions detected fungal hyphae in 93% and 100% of cases, respectively. As with cytology, sensitivity of histology for detection of fungal hyphae is highly dependent on the biopsy specimen. It usually requires sampling fungal plaques rather than adjacent mucosa or erroneously identified plaque-like exudate or necrotic debris.
Culture
Recent data demonstrated fungal cultures to be 100% specific for diagnosis of sinonasal aspergillosis in dogs with nasal discharge. Suboptimal laboratory methodology and inability to obtain appropriate nasal specimens most likely contributed to earlier low sensitivities. A recent study has shown that increasing the incubation temperature from room temperature to 37° C not only enhanced the sensitivity of fungal culture but also shortened time until fungal growth. The type of nasal sample obtained is of major importance. Sensitivity is the highest when fungal plaques are sampled (88%) followed by mucosal biopsies (75%). Blind endonasal swab samples are completely unreliable (19%) for diagnosing sinonasal aspergillosis.
Serology
Tests detecting serum Aspergillus-specific antibodies use commercially available, standardized, highly purified Aspergillus antigen solutions. However, only a few studies have evaluated the diagnostic value of these standardized solutions in canine sinonasal aspergillosis. The agar-gel double immunodiffusion is a highly specific (98 to 100%) but poorly sensitive (57 to 76.5%) diagnostic method, while enzyme-linked immunosorbent assay (ELISA) yields a higher sensitivity (88.2%) with equal specificity (96.8%). Due to its moderate sensitivity, serology is generally not regarded as an effective screening method for diagnosing sinonasal aspergillosis in dogs with chronic nasal discharge. Serum galactomannan antigen (a cell wall component released during fungal growth) and quantitative whole blood or nasal tissue fungal DNA detection are not reliable for diagnosis of canine sinonasal aspergillosis.
Treatment of Aspergillosis in Dogs
Effective treatment of sinonasal aspergillosis remains challenging despite various available therapeutic options, including orally administered systemic therapy, topical application of antifungal solutions and more invasive surgical procedures.
Antifungal Drugs
Antifungal drugs that are used for treating sinonasal aspergillosis belong to the azole group: the second-generation imidazoles (ketoconazole, clotrimazole, enilconazole) and the more potent third-generation triazoles (itraconazole, fluconazole). Through interaction with the fungal cytochrome P450 system, their primary mechanism of action is blocking synthesis of ergosterol, a key component of fungal cytoplasmic membranes.
Many azoles also interact with mammalian P450 isoenzymes responsible for side-effects (Hepatotoxicosis, anorexia, vomiting) and some drug interactions. Triazole drugs are more specific in targeting fungal cytochrome P450 with fewer side-effects. Because of poor to moderate efficacy, need for long-term administration (2-3 months), side-effects and cost, oral systemic therapy is not recommended as single therapy for sinonasal aspergillosis. The use of topical antifungal administration is the most widely used method of therapy. However, systemic therapy may still be indicated as part of the treatment regimen in cases of extra-nasal extension of the disease.
Topical Drug Choices
Topical therapy mainly includes use of enilconazole and clotrimazole because of their poor solubility. To avoid severe local side-effects, only polyethylene glycol-based clotrimazole solutions should be used for intranasal infusion. Enilconazole has the advantage of being less toxic, less irritating, and is active in the vapor phase over a distance of up to 1 cm.
Debridement and Infusion Therapy
Various procedures have been developed to administer antifungal agents topically. The recommended mode of administration uses meticulous debridement of sinonasal cavities followed by 1-hour infusion of 1% clotrimazole or 1-2% enilconazole through blindly placed catheters into each nasal cavity or through an endoscopically placed catheter into the nasal cavity and affected sinus. This procedure has the advantage of being non-invasive and has now replaced the older technique necessitating implantation of the infusion catheters into the sinus and nasal cavities via temporary sinus trephination.
Temporary Trephination and Infusion
As topical infusion techniques require long-lasting anaesthesia (mean: 2 h), a shorter but more invasive technique requiring temporary trephination of the frontal sinuses has been developed. This method consists of a 5 minute 1% clotrimazole flush followed by a depot of 1% clotrimazole cream (10-20g) in the frontal sinuses.
Viscosity of the cream provides greater retention time in the frontal sinus than the solutions used during infusion procedures, thereby increasing drug contact time with fungal elements despite a shorter anaesthesic. The average duration of anaesthesia is reported to be reduced to 30 minutes. An alternative approach involves combining endoscopic debridement with a 1-hour infusion of 2% enilconazole, followed by the application of 1% bifonazole cream into the affected frontal sinus via an endoscopically placed catheter.
Infusion Complications
Leakage of antifungal drugs at the level of the trephination holes or around the infusion catheters is common and usually without adverse effect. Perforation of the cribriform plate, in contrast, could allow leakage of antifungal solutions into the cerebral cavity, inducing meningoencephalitis and cortical signs that can include seizures, altered mental status, or even death. Infusions have been administered to a few dogs with a damaged cribriform plate without complication. Development of mucosal blebs and/or scar tissue formation after enilconazole infusion has been reported but does not appear to have clinical relevance apart from occasional obstruction of the nasal-frontal opening. Rarely, a nasal tumour has developed after intranasal enilconazole or clotrimazole infusion/depot.
Surgical Treatment Several surgical techniques have been described. They consist of rhinotomy, extensive debridement, and then topical application of povidone-iodine 10% “paint,” povidone-iodine impregnated dressings, or enilconazole 2% soak. All procedures result in favourable outcomes. Surgery can be quite destructive and should be used only in dogs with fungal lesions that cannot be otherwise debrided, in patients with cribriform plate damage, or refractory cases. Care must be taken to cause as little damage as possible to nasal mucosa and turbinectomy should be avoided. Finally, bone flap replacement after rhinotomy is not recommended.
Surgical Treatment
Several surgical techniques have been described. They consist of rhinotomy, extensive debridement, and then topical application of povidone-iodine 10% “paint,” povidone-iodine impregnated dressings, or enilconazole 2% soak. All procedures result in favourable outcomes. Surgery can be quite destructive and should be used only in dogs with fungal lesions that cannot be otherwise debrided, in patients with cribriform plate damage, or refractory cases. Care must be taken to cause as little damage as possible to nasal mucosa and turbinectomy should be avoided. Finally, bone flap replacement after rhinotomy is not recommended.
Treatment Response to Aspergillosis in Dogs
Assessing treatment response for aspergillosis in dogs is challenging. Disappearance of clinical signs 1-2 weeks post-therapy is not necessarily indicative of a long-term cure. Serial serum Aspergillus-specific antibody titres are not reliable, as they decline slowly, and positive results may persist for years, even in dogs that remain disease-free. Although CT imaging has not been thoroughly evaluated for this purpose, it is unlikely to distinguish between cure and persistent disease, as nasal cavity changes and bone hyperostosis often remain.
The most reliable method to assess treatment efficacy is an endoscopic re-examination of the sinonasal cavities within one month post-treatment. This can be done via flexible endoscope passage through the nasal-frontal opening or observation through a trephine hole. Absence of fungal colonies in the sinonasal cavities strongly suggests a cure.
Treatment success rates from studies on topical therapy show a mean first treatment success rate of 60% (range: 40-86%). However, multiple treatments (often 2) are typically required for complete resolution of the infection, with an overall global treatment efficacy of 92% (range: 83-100%). Treatment success is often higher in younger dogs, while chronic signs, bilateral disease, and adjunctive systemic antifungal therapy are associated with first treatment failure—likely due to worse disease at diagnosis. In some cases, where only focal disease and mild turbinate destruction are present, accessing infected areas may be difficult, leading to incomplete debridement and poor outcomes.
Treatment failure is likely multifactorial, but the ability to effectively debride fungal plaques is a key factor in treatment success. Antifungal resistance is not considered significant for canine sinonasal aspergillosis (SNA), as high concentrations of antifungal agents are achieved with topical treatments.
Long-Term Outcome of Aspergillosis in Dogs
Long-term outcomes following “successful” topical therapy for aspergillosis in dogs have been explored in only a few studies. In one study, with follow-up periods ranging from 5 to 64 months, 52% of dogs experienced episodic or permanent mild to moderate nasal discharge and/or sneezing. Another study, with follow-up periods ranging from 1.5 to 108 months, found that only 11% of dogs remained completely free of clinical signs, while others showed occasional sneezing and/or nasal discharge.
This persistent nasal discomfort is likely due to extensive and irreversible turbinate destruction, which may predispose dogs to chronic lymphoplasmacytic rhinosinusitis or secondary bacterial infections. Some dogs responded well to treatment with local glucocorticoids or antimicrobials to manage these complications. Recurrence of sinonasal aspergillosis (SNA) has been noted 2 months to 4 years after successful treatment. In some cases, the short interval between cure and recurrence suggests that a persistent fungal infection may have been missed during follow-up examinations, though reinfection cannot be definitively ruled out.
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