Intranasal infusion of enilconazole for treatment of sinonasal aspergillosis in dogs

OBJECTIVE: To determine effectiveness of infusion of 1 and 2% enilconazole for treatment of nasal and sinusal aspergillosis, respectively, in dogs. DESIGN: Case series. ANIMALS: 26 client-owned dogs with aspergillosis. PROCEDURE: All dogs had typical clinical signs of aspergillosis and rhinoscopically visible intrasinusal or intranasal fungal plaques associated with turbinate destruction. During rhinoscopy, affected nasal cavities and frontal sinuses were debrided meticulously. Nineteen dogs (group A) were treated with 1% enilconazole by use of a modified noninvasive infusion procedure. Seven dogs (group B) were treated with 2% enilconazole via catheters that were placed via endoscopic guidance into the frontal sinuses. All dogs underwent follow-up rhinoscopy for determination of further treatment until cure was established. RESULTS: Age, disease duration, clinical score, and rhinoscopic score were similar for both groups before treatment. In group A, 17 of 19 dogs were cured; 9, 6, and 2 dogs were cured after 1, 2, or 3 treatments, respectively. The remaining 2 dogs were euthanatized before the end of the treatment protocol. In group B, all dogs were cured; 6 dogs and 1 dog were cured after 1 or 2 treatments, respectively. Only minor adverse effects such as nasal discharge, epistaxis, and sneezing developed. CONCLUSIONS AND CLINICAL RELEVANCE: After extensive rhinoscopic debridement, 1 and 2% enilconazole infused into the nasal cavities and the frontal sinuses, respectively, were effective for treatment of aspergillosis in dogs. Intrasinusal administration via endoscopically placed catheters appeared to require fewer infusions for success. Follow-up rhinoscopy is strongly advised.     

Treatment of Canine Nasal Aspergillosis with Enilconazole

Twenty-four dogs with nasal aspergillosis were treated with enilconazole (10 mg/kg bid for 7–14 days) administered topically through tubes surgically implanted into the nasal chambers. Aspergillosis was eliminated in 19 dogs over a median follow-up period of 18 months. Another dog died, but at necropsy there was no evidence of causative fungus. Two of the four dogs that were not cured had infection of periorbital soft tissues. An additional seven dogs received 6 weeks ketoconazole (5 mg/kg bid PO) and enilconazole therapy topically. Six of these dogs were disease-free over a median follow-up period of 35 months. The seventh dog responded to repeated treatment with enilconazole. Twenty-six of the 29 dogs (90%)without extranasal aspergillosis were cured.     

Surgical treatment of canine nasal aspergillosis by rhinotomy combined with enilconazole infusion and oral itraconazole

OBJECTIVES: To evaluate the effectiveness of rhinotomy and surgical debridement associated with topical administration of 2 per cent enilconazole and oral itraconazole in dogs with severe or recurrent sinonasal aspergillosis. METHODS: A standard rhinotomy was performed on seven dogs. In the initial study, the bone flap was left attached cranially and replaced at the end of the procedure. In the main study group, the bone flap was discarded. Nasal passages were debrided and irrigated with enilconazole solution for one hour. Oral itraconazole was administered to four dogs for one month postoperatively. Follow-up rhinoscopy was performed in all dogs. RESULTS: All three dogs in the initial study had recurrence of the disease and two dogs had a second surgery to remove the flap. The main study group included four dogs in which the flap was initially removed, and the two dogs from the initial study that required a second surgery. At follow-up rhinoscopy, five dogs were free of aspergillus but had bacterial or inflammatory rhinitis and one dog had a small aspergilloma but was subsequently asymptomatic. Telephone follow-up revealed that four dogs were asymptomatic, one dog had intermittent sneezing and serous nasal discharge, and one dog had intermittent epistaxis. CLINICAL SIGNIFICANCE: Rhinotomy with removal of the flap combined with one-hour infusion of 2 per cent enilconazole and oral itraconazole resulted in satisfactory outcome in dogs with severe or recurrent aspergillosis.     

Efficacy of intrasinusal administration of bifonazole cream alone or in combination with enilconazole irrigation in canine sino-nasal aspergillosis: 17 cases

This study evaluated the effect of 1% bifonazole cream in the treatment of canine sino-nasal aspergillosis (SNA). The cream was instilled through perendoscopically placed catheters into the frontal sinuses and was used either as single therapy after debridement (DC) or as adjunctive therapy after 2% enilconazole infusion (DEC). Twelve dogs were treated initially with DEC: 7 and 3 of these dogs were free of disease after 1 and 2 procedures, respectively, while 2 dogs were cured after DC was used as a second procedure. Five dogs were treated with DC only: in 3 dogs with moderate disease, cure was obtained after a single procedure while, in 2 debilitated patients, cure could not be confirmed. Topical administration of 1% bifonazole cream appears as an effective therapy in SNA, either as an adjunctive therapy to enilconazole infusion or as sole therapy in moderately affected patients.     

Treatment of canine nasal aspergillosis with a new non-invasive technique. Failure with enilconazole

A new, non-Invasive technique recently described for the treatment of canine nasal aspergillosis was performed on four dogs. The antimycotic agent used was a 10 per cent enilconazole suspension, with the drug left in situ for a period of one hour. None of the dogs responded to single treatment. One dog died from an acute septic response secondary to pyelonephritis and bacterial endocarditis eight days after a second treatment. A second dog responded completely to a second treatment and remained free of fungal disease for a follow-up period of H months. In the remaining two dogs, extensive and profuse fungal growth was seen on rhinoscopic reexamination. Conventional treatment, with tube Implantation into the frontal sinuses and nasal irrigation for two weeks, was performed. Successful resolution of infection was obtained. Although the new, non-invasive technique was simple to carry out and well tolerated by the dogs, instillation of 10 per cent enilconazole appears to have poor therapeutic efficacy and exacerbated fungal growth in two of the animals.     

Update on canine sinonasal aspergillosis.

Sinonasal aspergillosis is a frequent cause of nasal discharge that occurs in otherwise healthy, young to middle-aged dogs. A local immune dysfunction is suspected in affected animals, and the role of increased interleukin-10 mRNA expression in the nasal mucosa of affected dogs is currently under investigation. Despite recent advances in imaging techniques, the "gold standard" for diagnosing the disease is direct visualization of fungal plaques during endoscopy or observation of fungal elements on cytology or histopathologic examination. Treatment can be challenging; however, the use of topical enilconazole or clotrimazole through noninvasive techniques has increased the success of treatment and decreased the morbidity and duration of hospitalization.     

Combined clotrimazole irrigation and depot therapy for canine nasal aspergillosis

OBJECTIVES: To evaluate the effect of short duration 1 per cent clotrimazole flush when combined with 1 per cent clotrimazole cream instilled into the frontal sinuses for the treatment of nasal aspergillosis in 14 dogs. METHODS: Fourteen dogs with clinical, radiological, serological and rhinoscopic findings consistent with nasal aspergillosis were treated by frontal sinus trephination and a short, five-minute flushing of 1 per cent topical clotrimazole solution followed by a 1 per cent clotrimazole cream instilled as a depot agent. RESULTS: Twelve of the 14 dogs (86 per cent) responded well to treatment and either had no clinical signs after treatment or had signs consistent with mild rhinitis during a minimum follow-up period of six months. Only one dog required multiple treatments. Treatment was well tolerated by all patients, with minimal complications. CLINICAL SIGNIFICANCE: This treatment compares favourably to previously published data using one-hour topical clotrimazole or enilconazole flushing treatment protocols. The treatment technique significantly reduced treatment time under anaesthesia.     

Clotrimazole and enilconazole distribution within the frontal sinuses and nasal cavity of nine dogs with sinonasal aspergillosis

Objectives: Multiple topical treatments are often required for clinical cure of mycotic rhinosinusitis in dogs. The objective of this study was to describe the distribution and retention of enilconazole and clotrimazole solutions using a temporary trephination protocol. Methods: Nine client-owned dogs diagnosed with mycotic rhinosinusitis between March 2008 and December 2009 were prospectively enrolled and were sequentially allocated to receive treatment with either clotrimazole (1% in polyethylene glycol) or enilconazole (10% solution), after imaging and rhinoscopic assessment. Both frontal sinuses were trephined, debrided and flushed with saline. Infusion was administered via frontal sinuses with dogs in sternal recumbency and computed tomography (CT) performed 5 minutes after completion. Distribution was scored 1 to 4 at the canine tooth, premolar 4, cribriform plate and frontal sinus on both sides, for a maximum score of 32. Results: Distribution of antifungal agents to all regions of the nasal cavity and frontal sinuses was achievable, but varied considerably. Retention was poor in 10 of 18 regions assessed. Clinical Significance: Distribution of antifungal agents within the frontal sinuses is achievable using temporary trephination; however, distribution is variable and retention is often poor.     

COMPARISON OF RADIOGRAPHY AND COMPUTED TOMOGRAPHY FOR THE DIAGNOSIS OF CANINE NASAL ASPERGILLOSIS

To compare the radiographic and computed tomographic (CT) findings and to evaluate the sensitivity of radiography and CT for diagnosis of nasal aspergillosis in dogs, the radiographic and CT studies of 48 dogs with chronic nasal disease were reviewed separately. The radiographic and CT findings were recorded, and a diagnosis was made. The results obtained in the dogs with nasal aspergillosis (n = 25) were used. Based on definite aspergillosis as diagnosis, CT had a sensitivity of 88% and radiography of 72%. Considering definite and probable aspergillosis as equivalent, CT had a sensitivity of 92% and radiography of 84%. The sensitivity was higher in dogs with lesions affecting the entire nasal cavity and frontal sinus on at least one side (n = 20) with a sensitivity of 100% for CT and 90-95% for radiography than in dogs with lesions restricted to the nasal cavities (n = 5) where CT had a sensitivity of 60-80% and radiography of 0-40%. CT was superior to radiography for evaluation of the nasal cavities (mucosal thickening along the nasal bones, surrounding bone hyperostosis/lysis), frontal sinuses (mucosal thickening along the frontal bone, fluid/soft tissue, frontal bone hyperostosis/lysis), and differentiation between a cavitated-like or a mass-like process. This study suggests that CT is more sensitive than radiography for diagnosis of nasal aspergillosis in the dog because of a better demonstration of some changes suggestive of nasal aspergillosis. A diagnosis of a nasal aspergillosis restricted to the nasal cavities or associated with an FB is challenging, even with the use of CT.     

Radiographic, magnetic resonance imaging, computed tomographic, and rhinoscopic features of nasal aspergillosis in dogs

OBJECTIVE: To determine radiographic, magnetic resonance imaging (MRI), computed tomography (CT), and rhinoscopic features of nasal aspergillosis in dogs. DESIGN: Prospective study. ANIMALS: 15 client-owned dogs. PROCEDURE: All dogs had clinical signs of chronic nasal disease; the diagnosis of nasal aspergillosis was made on the basis of positive results for at least 2 diagnostic tests (serology, cytology, histology, or fungal culture) and detection of typical intrasinusal and intranasal fungal colonies and turbinate destruction via rhinoscopy. Radiography, MRI, and CT were performed under general anesthesia. Rhinoscopy was repeated to evaluate lesions and initiate treatment. Findings of radiography, MRI, CT, and rhinoscopy were compared. RESULTS: MRI and CT revealed lesions suggestive of nasal aspergillosis more frequently than did radiography. Computed tomography was the best technique for detection of cortical bone lesions; the nature of abnormal soft tissue, however, could not be identified. Magnetic resonance imaging allowed evaluation of lesions of the frontal bone and was especially useful for differentiating between a thickened mucosa and secretions or fungal colonies; however, fungal colonies could not be differentiated from secretions. Rhinoscopy allowed identification of the nature of intranasal and intrasinusal soft tissue but was not as useful as CT and MRI for defining the extent of lesions and provided no information regarding bone lesions. CONCLUSIONS AND CLINICAL RELEVANCE: The value of CT and MRI for diagnosis of nasal aspergillosis was similar and greater than that of radiography. Rhinoscopy is necessary because it is the only technique that allows direct visualization of fungal colonies.     

Long-term outcomes in dogs with sinonasal aspergillosis treated with intranasal infusions of enilconazole

Long-term outcomes (mean 38+/-17 months) were evaluated in 27 dogs with sinonasal aspergillosis after successful medical treatment using intranasal infusions of 1% or 2% enilconazole (1%, n=15; 2%, n=12). Long-term outcomes with both treatment protocols were good, with half of the dogs being asymptomatic throughout the follow-up period. The remaining dogs showed mild clinical signs compatible with chronic rhinitis/sinusitis. These clinical signs were interpreted as chronic lymphoplasmacytic rhinitis/sinusitis and episodes of bacterial rather than fungal infection. Three dogs had confirmed reinfection or relapse 2 to 36 months after clinical resolution.     

Canine nasal aspergillosis

Chronic nasal discharge is a common clinical sign of disease in dogs. Canine sinonasal aspergillosis is a relatively common disease in dogs. The three hallmarks of canine nasal aspergillosis are a profuse mucoid to hemorrhagic chronic nasal discharge that may alternate with periods of epistaxis, ulceration of the external nares with crusting, and pain or discomfort in the facial region. Diagnostic imaging (preferably computed tomography, CT) of the nasal cavity and paranasal sinuses is an important component of the evaluation of dogs with signs of nasal disease. Rhinoscopy is an important part of both the diagnosis and the therapy for nasal aspergillosis. Therapeutic recommendations for sinonasal aspergillosis have included surgery and the use of several systemic and topical antifungal drugs.     

COMPUTED TOMOGRAPHIC FINDINGS IN 35 DOGS WITH NASAL ASPERGILLOSIS

The purpose of this study was to describe the computed tomographic (CT) features of nasal aspergillosis in dogs. Initial (n = 35) and follow-up (n = 12) CT images were available from 35 dogs. The most commonly encountered CT findings were (1) moderate to severe cavitary destruction of the turbinates with presence of a variable amount of abnormal soft tissue in the nasal passages, (2) non-specific thickening of the mucosa adjacent to the inner surface of bones of the frontal sinus, maxillary recess and nasal cavity and, (3) thickened reactive bone. The findings were consistent with a disease initially affecting one nasal cavity then progressing into the ipsilateral frontal sinus, the contralateral nasal cavity and the contralateral frontal sinus. Two dogs with associated nasal foreign body had a more localized invasion of the nasal cavity. Attenuation values and contrast enhancement were not specific. With follow-up examinations, a reduction in the amount of abnormal soft tissue was observed in all dogs except one, but this reduction could not be quantified.     

DIAGNOSTIC VALUE OF COMPUTED TOMOGRAPHY IN DOGS WITH CHRONIC NASAL DISEASE

Computed tomographic (CT) studies of 80 dogs with chronic nasal disease (nasal neoplasia (n = 19), nasal aspergillosis (n = 46), nonspecific rhinitis (n = 11), and foreign body rhinitis (n = 4)) were reviewed retrospectively by two independent observers. Each observer filled out a custom-designed list to record his or her interpretation of the CT signs and selected a diagnosis. Accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for the diagnosis of each disease. The agreement between observers was evaluated. The CT signs corresponded to those previously described in the literature. CT had an accuracy greater than 90% for each observer in all disease processes. The sensitivity, specificity, PPV, and NPV were greater than 80% in all dogs with the exception of the PPV of foreign body rhinitis (80% for observer A and 44% for observer B). There was a substantial, to almost perfect, agreement between the two observers regarding the CT signs and diagnosis. This study indicates a high accuracy of CT for diagnosis of dogs with chronic nasal disease. The differentiation between nasal aspergillosis restricted to the nasal passages and foreign body rhinitis may be difficult when the foreign body is not visible.     

Use of ketoconazole in the treatment of canine nasal aspergillosis

Fifteen dogs with nasal aspergillosis were treated with ketoconazole (5 mg/kg of body weight, q 12 h, PO) for 2 to 18 weeks. Four dogs whose conditions deteriorated during treatment received ketoconazole for less than the prescribed 6 weeks. Six months or more later, only 47% of the dogs were determined to be disease-free, on the basis of no fungal growth on culture. It was concluded that ketoconazole at this dosage is a useful treatment for canine nasal aspergillosis, but is no more effective than thiabendazole.     

Comparison of serologic evaluation via agar gel immunodiffusion and fungal culture of tissue for diagnosis of nasal aspergillosis in dogs

OBJECTIVE: To compare the sensitivity and specificity of serologic evaluation and fungal culture of tissue for diagnosis of nasal aspergillosis in dogs. DESIGN: Prospective study. ANIMALS: 58 dogs with nasal discharge and 26 healthy dogs. PROCEDURES: Dogs with nasal discharge were anesthetized and underwent computed tomography and rhinoscopy; nasal tissues were collected for histologic examination and fungal culture. Sera were assessed for antibodies against Aspergillus spp (healthy dog sera were used as negative control specimens). Nasal aspergillosis was diagnosed in dogs that had at least 2 of the following findings: computed tomographic characteristics consistent with aspergillosis, fungal plaques detected during rhinoscopy, and histologically detectable fungal hyphae in nasal tissue. Histologic characteristics of malignancy were diagnostic for neoplasia. Without evidence of neoplasia or fungal disease, nonfungal rhinitis was diagnosed. RESULTS: Among the 58 dogs, 21 had nasal aspergillosis, 25 had nonfungal rhinitis, and 12 had nasal neoplasia. Fourteen aspergillosis-affected dogs and 1 dog with nonfungal rhinitis had serum antibodies against Aspergillus spp. Fungal culture results were positive for Aspergillus spp only for 17 dogs with aspergillosis. With regard to aspergillosis diagnosis, sensitivity, specificity, and positive and negative predictive values were 67%, 98%, 93%, and 84%, respectively, for serum anti-Aspergillus antibody determination and 81%, 100%, 100%, and 90%, respectively, for fungal culture. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that seropositivity for Aspergillus spp and identification of Aspergillus spp in cultures of nasal tissue are highly suggestive of nasal aspergillosis in dogs; however, negative test results do not rule out nasal aspergillosis.     

Enilconazole treatment of horses with superficial Aspergillus spp. rhinitis

BACKGROUND: Mycotic rhinitis is an uncommon disease in horses with a wide range of clinical signs and treatment options based on case studies of a single or only a few individuals. Moreover, while dogs with mycotic rhinitis appear to respond well to treatment with topical enilconazole, this approach has yet to be reported in horses. OBJECTIVES: The aim of this study was to describe the clinical findings, results of diagnostic investigations, treatment, and outcome in horses with mycotic rhinitis treated with topical enilconazole. ANIMALS: Eight horses were included in the study. METHODS: Medical records from 1995 to 2007 from an equine veterinary teaching hospital were reviewed to identify cases with a diagnosis of mycotic rhinitis. RESULTS: Eleven cases were identified, of which 8 were treated with topical enilconazole. Seven of those 8 horses recovered and had normal appearance of the nasal passages on endoscopic examination. Fungal culture, where positive, yielded only Aspergillus spp. Treatment was readily performed and no adverse effects were noted in these horses. In 5 horses, long-term follow-up revealed complete recovery for an average of 5 years. CONCLUSIONS AND CLINICAL IMPORTANCE: Mycotic rhinitis owing to Aspergillus spp. in horses can be effectively and safely treated with topical enilconazole.     

Nasal aspergillosis and penicilliosis in dogs: results of treatment with thiabendazole

Forty-seven dogs with nasal aspergillosis or penicilliosis were treated with thiabendazole (20 mg/kg orally for 6 weeks). Nasal turbinectomy was performed on 26 of the dogs. Six months or more later, 43% of the dogs were clinically normal or considerably improved; results were better in dogs not treated surgically. It was concluded that thiabendazole at a dosage of 20 mg/kg is not an effective treatment for nasal aspergillosis or penicilliosis in dogs.     

Open Nasal Cavity and Frontal Sinus Treatment of Chronic Canine Aspergillosis

Five dogs with nasal aspergillosis were treated by surgical exposure and delayed closure of the nasal cavity and involved frontal sinus. Diseased tissue was excised, and 10% povidone-iodine solution was applied three times daily with cotton-tipped applicators. Skin wounds were closed at weeks 6 through 8. In one dog, the frontal sinus was partially obliterated with a temporalis muscle flap before skin closure. At months 6 through 34, all dogs were clinically free of aspergillosis. Open treatment has potential clinical application as a primary approach to nasal aspergillosis or for cases that are unresponsive to previous medical management.     

Acute phase protein concentrations in dogs with nasal disease

The concentrations of C-reactive protein (CRP), serum amyloid A, haptoglobin (Hp) and α(1)-acid glycoprotein were measured in dogs with clinical signs of nasal disease and compared with those of healthy dogs in order to determine the expression of these proteins in cases of canine nasal disease. A significant difference (P<0.001) between the symptomatic group and the control group was found for both CRP and Hp. Among the animals with nasal disease, a significant intergroup difference (P<0.05) was found in the expression of Hp between dogs with aspergillosis and those with chronic rhinitis.