Treatment of Sinonasal Aspergillosis by Debridement and Sinonasal Deposition Therapy with Clotrimazole Under Rhinoscopic Guidance
ABSTRACT
Rhinoscopy was performed on 10 dogs with sinonasal aspergillosis (SNA). Direct access to the sinus via the nasal ostium was possible with a flexible endoscope to allow sinuscopy. Debridement of fungal plaques in the frontal sinus and the nasal cavity was performed, and a sinus and nasal deposition therapy with clotrimazole (1%) cream was made under rhinoscopic guidance. No oral medication was administered following the procedure. A rhinoscopic follow-up was performed monthly until cure. Six of ten (60%) dogs presented fungal plaques in the nasal cavity and in the frontal sinus and 4/10 (40%) dogs presented fungal plaques only in the frontal sinus. Five of ten (50%) dogs were considered to be cured at the first follow-up rhinoscopy, 4/10 (40%) after the second follow-up, and 1/10 (10%) after the third. Two dogs had delayed recurrence of SNA rhinoscopically assessed 12 and 21 mo, respectively, after the last clotrimazole treatment. Endoscopic debridement of fungal plaques and clotrimazole (1%) cream deposition therapy seems to be a valuable minimally invasive technique for SNA treatment in dogs without the use of complementary oral medication. Delayed recurrence is a potential finding following treatment of SNA.
Introduction
Sinonasal aspergillosis (SNA) is a common and severe disease in dogs, causing rhinitis and sinusitis. Clinical signs include chronic mucopurulent to purulent nasal discharge, nasal pain, nasal planum ulceration and/or depigmentation, sneezing, and epistaxis. Facial deformity, epiphora, and seizures may be identified in severe cases of SNA. Systemic signs such as anorexia and depression may be observed.1–3 Sinonasal aspergillosis may be suspected on the basis of history and physical examination, via rhinoscopy, radiography, computed tomography, magnetic resonance imaging, mycological culture, and serology.2–8
Systemic and topical treatments of canine SNA have been proposed.3 Topical antifungal administration remains the most widely used method of treatment in dogs, with a greater success rate presumed to be because of direct action on fungal plaques.2,3 Original topical therapeutic techniques involved instillation of enilconazole via catheters surgically implanted into the nasal cavity.6,9,10 The need for repetitive administration (twice daily for 7–14 days) led to the declining popularity of these methods. Frontal sinus trephination for temporary catheterisation, and noninvasive protocols without trephination allowed frontal sinus distribution of the antifungal agents and the assessment of sinonasal ostium patency.6,11–17 Combined trephination, short clotrimazole soak, and application of clotrimazole cream to the frontal sinuses was developed to reduce procedure time.1,14 The application of a cream that is more viscous than a liquid was postulated to improve antifungal agent retention, thus improving contact time and treatment success. To avoid morbidity of the trephination, a sinusal deposition therapy using catheters placed into the frontal sinus under endoscopic guidance was proposed.18 The debridement of the fungal plaques prior to the application of topical treatment was proposed to improve results. It can be carried out following frontal sinus trephination, rhinotomy, or with a minimally invasive approach.14,18–20 Endoscopic debridement alone is often a successful treatment in humans with chronic, erosive mycotic rhinosinusitis and may also be an important aspect of therapy in dogs.21
The purpose of this study was to describe a treatment of canine SNA that includes the rhinoscopic debridement of the fungal plaques, a deposition therapy of clotrimazole (1%) cream perendoscopically instilled into the frontal sinuses and nasal cavities, the avoidance of complementary oral medication following the procedure, and a systematic rhinoscopic follow-up.
Materials and Methods
Ten dogs who presented with SNA between January 2011 and December 2014 were included in the study. The diagnosis was based on the presence of clinical findings (nasal discharge, nasal pain, nasal planum ulceration and/or depigmentation, sneezing, and epistaxis), endoscopic observation of fungal plaques associated with turbinate destruction, and/or fungal culture.
A standardized protocol of SNA treatment had previously been developed with clinical cases that were not included in this prospective study. It included (1) the debridement of the fungal plaques in the nasal cavities and the frontal sinuses under endoscopic guidance, (2) a deposition therapy of clotrimazole (1%) cream instilled perendoscopically into the frontal sinuses and nasal cavities; (3) the avoidance of complementary oral medication following the procedure; and (4) a rhinoscopic follow-up performed monthly until cure. This protocol was carried out in all the cases included in the study.
Criteria for inclusion in the study were the confirmation of an SNA and the involvement of both the nasal cavity and the frontal sinus. Our protocol needs sinonasal ostium catheterization to perform debridement and deposition therapy in the frontal sinus. Access here is only possible because of the secondary aspergillosis tissue degradation that increases the ostium’s diameter in the case of sinus involvement. In cases in which only the nasal cavity is involved, ostium diameter is not altered and does not allow its catheterization (personal observation). By contrast, catheterization of the ostium is possible in all cases of SNA that affect the frontal sinus and does not represent a limiting condition for achieving the treatment. We excluded from the study the dogs who did not have a complete rhinoscopic follow-up and at least 6 mo of telephonic follow-up, and dogs with neurological abnormalities that could suppose involvement of the cribiform plate. This event could be associated with a risk of adverse secondary effects due to the passage of the clotrimazole cream to the brain.
Breed, sex, age, clinical signs, presence of unilateral or bilateral involvement, duration of clinical signs before inclusion in the study, and previous treatment received were recorded.
Dogs were anesthetized during the procedure. Premedication was made with morphinea (0.1–0.3 mg/kg) or butorphanolb (0.25 mg/kg) associated with medetomidinc (5–10 µg/kg), acepromazind (0.05–01 mg/kg), or midazolame (0.1–0.5 mg/kg). Induction was made with propofolf (1–4 mg/kg) or thiopentoneg (5–10 mg/kg). After intubation, anesthesia was maintained with isoflurane in oxygen.
Dogs were positioned in sternal recumbency. Both nasal cavities were explored with a flexible endoscopeh that allowed direct frontal sinus access via the sinonasal ostium (Figure 1). Screening of the nasal cavity and the frontal sinus was performed as a first step to enumerate and localize the fungal plaques (unilateral or bilateral involvement, sinus and/or nasal involvement).
Citation: Journal of the American Animal Hospital Association 54, 2; 10.5326/JAAHA-MS-6648
Endoscopically guided debridement was performed by means of forcepsi, suction catheters, and lavage with saline solution until entire fungal plaques and necrotic material were macroscopically removed from the nasal cavity (Figure 2) and/or the frontal sinus (Figure 3). Suction of fungal plaques was the preferred method of debridement because it was less aggressive than the use of forceps and decreased the risk of hemorrhage. Irrigation and local application of adrenalin were employed to reduce blood flow in case of severe hemorrhage. Flexible endoscopy allowed visualization of the entire nasal cavity and frontal sinus so complete debridement of fungal plaques could be macroscopically assessed. An 8-F oxygen catheterj was then placed into the frontal sinus under endoscopic guidance via the nasal cavity (Figure 4). Clotrimazole (1%) creamk was administered via the catheter until complete filling of the sinus (Figure 5). The catheter was subsequently removed from the sinus and clotrimazole was administered until complete filling of the nasal cavity. Compression of the nasopharynx was performed using gauze packing of the caudal oropharynx in order to avoid leakage of clotrimazole cream. The deposit was stopped when the cream was visible through the nostrils. The number of tubes of cream that were used was recorded. We only treated the affected side in case of unilateral macroscopic SNA confirmed by rhinoscopy and sinuscopy. Recording of the duration of the procedure was not prospectively planned in our protocol and was retrospectively estimated from the anesthetic reports.
Citation: Journal of the American Animal Hospital Association 54, 2; 10.5326/JAAHA-MS-6648
Citation: Journal of the American Animal Hospital Association 54, 2; 10.5326/JAAHA-MS-6648
Citation: Journal of the American Animal Hospital Association 54, 2; 10.5326/JAAHA-MS-6648
Citation: Journal of the American Animal Hospital Association 54, 2; 10.5326/JAAHA-MS-6648
Dogs were discharged from the clinic on the same day without any antimicrobial or antifungal medication.
Follow-up rhinoscopy was scheduled 4 wk after the initial treatment. If rhinoscopy did not show any signs of recurrence of fungal plaques in the nasal cavities or in the frontal sinuses, a second administration of clotrimazole was performed in the same manner as outlined above and the dog was considered to be cured. If signs of recurrence were present, localization of the fungal plaques was recorded, a debridement was performed in the same manner as previously described, and a further deposition therapy was performed. Rhinoscopic follow-up was scheduled monthly until the dog no longer showed sign of recurrence of the fungal plaques and was considered to be cured. Complementary telephone follow-up was intermittently made after the last rhinoscopy. Owners were surveyed regarding the duration of the persistence of the clotrimazole cream in the nasal discharge of their dogs after deposition therapy, and potential clinical signs of recurrence of SNA (nasal discharge, nasal pain, nasal planum ulceration and/or depigmentation, sneezing, and epistaxis) Total duration of follow-up was recorded.
Results
Ten dogs were included in the study; no exclusion criteria were encountered during the recruitment period. There were 3 Labrador retrievers, 2 rottweilers, 1 golden retriever, 1 Alaskan malamute, 1 fox terrier, 1 Beauce shepherd, and 1 Great Dane. There were 4 intact males and 6 females (of whom 3 were spayed). The mean age at the time of first consultation was 5.4 years (standard deviation [SD] = 2.5). Clinical signs were nasal discharge (100%), sneezing (60%), epistaxis (60%), nasal planum depigmentation (20%), and nasal planum ulceration (10%). No neurological signs were diagnosed. The duration of clinical signs prior to treatment in the current study ranged from 1 mo to several years. Two dogs had clinical signs of bilateral involvement at the time of consultation, of whom one had a history of unilateral chronic nasal discharge initially with a recent secondary involvement on the other side. Two dogs had been treated for SNA with noninvasive enilconazole soaks infusions, performed via nasal cavities catheterization three times without improvement (Table 1).
Fungal plaques were found in both the nasal cavity and the frontal sinus (60%) and in the frontal sinus without involvement of the nasal cavity (40%). Their appearance varied from white and fluffy to a purulent yellow. Rhinoscopic evaluation confirmed bilateral involvement in only one dog, the second one presented with bilateral nasal discharge showed unilateral involvement with a collapse of the nasal septum (Table 1). Depending on the size of the dog, two to five 20 g tubes of cream were used to fill a frontal sinus and a nasal cavity. This represents a quantity of 400–1000 mg of clotrimazole. The exact quantity of cream effectively used could not be measured on account of losses. The duration of the whole procedure was subjectively evaluated from the anesthetic report of the first rhinoscopies of each dog and was 45 min (SD = 10.8). The major variable of duration was the debridement phase that differed based on unilateral or bilateral involvement and presence or absence of fungal plaques in the nasal cavity (Table 2).
A first follow-up rhinoscopic evaluation was performed in all cases with a mean time of 26.3 days (SD = 10.5) between the two exams. Five dogs were considered to be cured on account of the absence of fungal plaque in the nasal cavity and the frontal sinus. A second follow-up rhinoscopic evaluation was performed in the five other dogs and one of the cured dogs who was diagnosed with a severe erosion of the nasal mucosa (there was concern regarding a possible osseous proliferation of the aspergillosis and we performed another follow-up as a precaution). The mean time between the first and the second follow-up was 28.8 days (SD = 9.7). Only one dog was diagnosed with fungal plaques at the second follow-up exam and was seen for a third follow-up rhinoscopy 25 days after with no evidence of persistence of the infection.
Owners reported evidence of the cream in the nasal discharge and sneezing several days after deposition therapy. The exact duration could not be statistically interpreted because several owners considered it impossible to assess the presence of the cream after 2 or 3 days because of dilution of the latter in the nasal discharge.
The total duration of follow-up was 18.4 mo (SD = 7.6) and was stopped at the time of writing the study. During the telephonic follow-up, two dogs presented clinical signs of recurrence of SNA that was observed by the owners and confirmed by rhinoscopy at 12 and 21 mo, respectively (Table 2). One of them had been treated with enilconazole infusion therapy without improvement prior to being included in the deposition therapy protocol.
Discussion
The present study describes and assesses feasibility of a standardized protocol in the treatment of canine SNA that includes (1) the endoscopic debridement of the fungal plaques; (2) a deposition therapy of clotrimazole (1%) cream instilled noninvasively into the frontal sinuses and nasal cavities; (3) the avoidance of complementary oral medication following the procedure; and (4) a systematic rhinoscopic follow-up.
Ten dogs were included in the study. All of them could be considered as mesocephalic or dolicocephalic breeds and were described as young to middle-aged (5.4 ± 2.5 yr).4,6 Only one of the dogs presented fungal plaques in both sides during the rhinoscopic evaluation. The second dog with a bilateral discharge was diagnosed with unilateral presence of fungal plaques and a rupture of the nasal septum.
Debridement of the fungal plaques is critical in curing mycotic rhinosinusitis in people.21 Johnson and others have reported that fungal plaques were present in the frontal sinus in 16 of 19 dogs who underwent sinuscopy.19 Extensive and adequate debridement of fungal plaques is therefore only likely to be possible with techniques aimed at direct access to the frontal sinuses. Debridement of fungal plaques may be underperformed in canine SNA, probably on account of the need for an aggressive procedure by way of trephination of the frontal sinus, or rhinotomy, to achieve it. Catheterization of the frontal sinus by flexible endoscopy is a less invasive technique and would be considered as the technique of choice to perform complete debridement of the fungal plaques in both the nasal cavity and the frontal sinus.2,6,14,18–20
The use of antifungal deposition therapy in the frontal sinus has already been described after trephination of the frontal sinus, or after catheterization of the frontal sinus under endoscopic guidance, but there is no report that describes a combined deposition therapy of both the frontal sinus and the nasal cavity as performed in our study.1,18 The viscosity of the preparation cream may provide greater persistence in the frontal sinus than an antifungal solution, thereby increasing drug contact time with the fungal colonies.1 In the study by Sissener et al., 10 g of clotrimazole cream was instilled into the sinus on each side in dogs weighing <10 kg, and 20 g was instilled per side in dogs weighing >20 kg.1 We proposed that filling of the frontal sinuses as well as the nasal cavities would further improve contact with residual fungal material and improve outcomes. Forty to one hundred g of clotrimazole cream was needed, depending on the size of the dog, to achieve the complete filling of both the frontal sinus and the nasal cavity per side. We only treated the affected side in case of unilateral SNA confirmed by rhinoscopy. It was not possible to quantify the exact duration of the persistence of the cream in the sinuses and the nasal cavities, but owners reported that their dogs had evidence of the cream in the nasal discharge and sneezing several days after rhinoscopy. A cadaveric study using the trephination of the frontal sinus and sinusal deposition therapy of clotrimazole reported that clotrimazole cream persisted in the frontal sinus at least 96 hr after administration.22 The use of clotrimazole cream in a deposition therapy was associated with a higher first treatment response rate (70% success) than a 1-hr “soak” with clotrimazole solution alone (40% success).23
There is only one report describing catheterization of the frontal sinus under endoscopic guidance to perform a deposition therapy with an antifungal cream agent.18 In this retrospective study, several procedures were mixed: 12 dogs received an enilconazole (2%) infusion before bifonazole (1%) cream deposit, and only 5 dogs were treated with deposition therapy as the sole treatment. In our study, all the dogs were managed with the same procedure: debridement of the fungal plaques and deposition therapy of clotrimazole (1%) cream in the involved frontal sinuses and nasal cavities. Billen and others considered a deposition therapy as the sole treatment for the debilitated patients and dogs with only moderate amounts of fungal materials.18 Our results show that the procedure may be valuable for a large population of patients with SNA. We did not encounter dogs with central nervous system symptoms in our recruitment period. We speculate that cribiform plate erosion would be associated with a risk of secondary adverse effects due to the passage of the topical treatment to the brain and we do not recommend the use of cream deposition for such cases.
It has been demonstrated that the use of a deposition therapy with an antifungal cream offered a reduced duration of treatment as compared with an infusion of an antifungal agent. The average duration of procedure in our study was 45 min. Duration of anesthesia for trephination was approximately 30 min, but the procedure did not include fungal plaques debridement that could be time-consuming in our practice.1 By comparison, an anesthesia period of no less than 60 min can be anticipated for other techniques.13
In the protocol of canine SNA treatment presented here, no complementary oral medication was used following rhinoscopy. It differs from others reports in which dogs received antimicrobials and/or antifungal drugs after deposition therapy.1,18 We postulated that adding oral systemic antifungal therapy to topical therapy was not necessary even if some authors think that it may enhance the efficacy of the treatment.10
A systematic follow-up rhinoscopy examination was made to ensure the effectiveness of the treatment in this study. Because clinical improvement was obvious after one treatment, persistence of fungal plaques can be easily missed without follow-up rhinoscopy. Additionally, bacterial rhinitis and sinusitis, frequent sequelae of extensive turbinate destruction, cannot be distinguished from persistent fungal infection. It has previously been demonstrated that the presence or lack of nasal discharge and the results of repeated serologic testing following the local treatment of canine SNA were not predictive of disease status.24 Rhinoscopy was therefore preferred for the detection of persistent disease.6 We classified dogs who had fungal plaques present at follow-up rhinoscopy as treatment failure even if a clinical improvement was noticed by the owners after deposition therapy. In a retrospective study of 23 dogs, follow-up rhinoscopy performed 1–4 mo following treatment with clotrimazole infusion reported 48% of dogs who were rhinoscopically free of fungal disease evidence.24 In our study, we confirmed the absence of fungal plaques in 50% of the dogs at the first follow-up rhinoscopy made 26.3 ± 10.5 days after initial treatment. The follow-up was made by rhinoscopic exams until the complete disappearance of fungal plaques and then by telephone (Table 2). Two dogs had delayed recurrence of SNA rhinoscopically assessed during the follow-up. The first dog was considered to be cured after the first follow-up rhinoscopy 12 mo prior to recurrence. The second dog had a recurrence 21 mo after the second follow-up rhinoscopy, which had shown no regrowth of the fungal plaques. This was the second failure of an SNA treatment encountered in this dog following a first attempt of enilconazole infusion therapy made 7 mo before the first clotrimazole deposition therapy. It was not possible to differentiate between a real recurrence and a new infection that appeared several months after the cure.
We reported 100% success after one (50 %), two (40 %) or three (10 %) therapeutic procedures. Even if the dogs were considered cured when performing the follow-up rhinoscopy, we decided to perform another cream deposit as a precaution. A dog with severe erosion of the nasal mucosa received another follow-up exam and deposit to prevent osseous proliferation of the aspergillosis. The treatment outcome in this study compares favorably with those previously reported for topical deposition therapy in SNA. Billen and others reported 100% success after one (7/10 dogs) or two (3/10 dogs) endoscopic debridement + enilconazole (2%) infusion + bifonazole (1%) deposition therapy procedures.18 Trephination of the frontal sinus and topical deposition therapy of clotrimazole cream was associated with 86% success rate.1 Nevertheless, the follow-up was only made by telephone without control rhinoscopy in these studies. If we consider the two recurrences of SNA, the global success rate was 80% in our study.
Conclusion
The association of the debridement of fungal plaques and deposition therapy of clotrimazole (1%) cream into the frontal sinus and the nasal cavity under endoscopic guidance provides a fast and effective treatment technique for canine SNA. This protocol is worthy of interest. Its effectiveness should be assessed with a larger randomized study including several protocols and the same rhinoscopic follow-up to compare the results of each treatment.
Rhinoscopy of the case n°1. The increased diameter of the sinonasal ostium allowed direct access to the frontal sinus.
Rhinoscopy of the case n°4 before (A) and after (B) debridement of the fungal plaques in the right nasal cavity.
Sinuscopy of the case n°6 before (A) and after (B) debridement of the fungal plaques in the left frontal sinus.
Rhinoscopy of the case n°1. Catheterization of the sinonasal ostium was performed with an 8-F oxygen catheter.
Sinuscopy of the case n°6. Catheterization of the frontal sinus was made through the sinonasal ostium (A) and deposition therapy of clotrimazole cream was made under endoscopic guidance (B).
Contributor Notes
