Sinonasal aspergillosis in dogs: a review

Sinonasal aspergillosis is an uncommon, yet debilitating and often frustrating condition to treat in dogs despite years of research evaluating pathogenesis, diagnosis and treatment. The disease is most commonly caused by non-invasive fungal infection, thought to be secondary to altered innate and/or adaptive immune responses. Attempts to confirm this have however failed. A variety of conflicting opinions regarding the diagnosis and treatment of sinonasal aspergillosis exist. Often the use of a particular treatment protocol is based upon personal or regional preference. Evaluation of the veterinary literature demonstrates that the evidence base in support of individual treatment recommendations is weak. A number of recent publications have helped to expand the current knowledge base and therefore our understanding of important practicalities for both diagnostic options and treatment protocols. The following review examines the current evidence for the pathogenesis of sinonasal aspergillosis in dogs, as well as the various diagnostic options. The available evidence for frequently utilised -therapeutic options and their likely outcomes is also explored.     

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.     

Disseminated aspergillosis in dogs

Clinical and pathological findings are reported from a series of 12 cases of disseminated aspergillosis (A. terreus) in 11 German Shepherd dogs and one Dalmatian referred to Murdoch University Veterinary Hospital (MUVH) over the period 1980 to 1984. A preliminary study of humoral and cell mediated immune components and complement levels revealed no consistent abnormality in 9 dogs tested apart from raised IgG levels. Serum IgA levels were depressed in 30% of cases. Serial data from one extensively monitored case is presented. The unusual epidemiological and pathogenetic features of the disease are discussed.     

Sinonasal and sino-orbital aspergillosis in 23 cats: aetiology, clinicopathological features and treatment outcomes

Aetiology, clinicopathological findings and treatment outcomes were documented in 23 cats (1.5-13 years of age) with sinonasal (SNA, n=6) or sino-orbital (SOA, n=17) aspergillosis. Cases recruited retrospectively and prospectively were included if fungal hyphae were identified on cytological or histological examination and the fungal pathogen was identified by PCR and DNA sequencing (ITS1 or ITS1-5.8S-ITS2 regions, rDNA gene cluster). Fungal culture was positive in 22/23 cases. In cases of SNA, the fungal pathogen was Aspergillus fumigatus (n=4), Neosartorya fischeri or A. lentulus (n=1) or a non-speciated Neosartorya spp. (n=1). In all cases of SOA (n=17), the fungal pathogen was identified as Neosartorya spp. Nine cats had brachycephalic conformation. Cats with SNA were more likely to be infected with A. fumigatus and had a better prognosis than cats with SOA.     

Cullen frontal sinus valved glaucoma shunt: preliminary findings in dogs with primary glaucoma

PURPOSE: To evaluate the efficacy of a novel, professionally manufactured, frontal sinus valved glaucoma shunt in maintaining normal intraocular pressure (IOP) and vision in dogs with primary glaucoma. METHODS: Three eyes of three dogs diagnosed with primary glaucoma were included in this prospective clinical study. A Cullen frontal sinus valved glaucoma shunt was implanted into each glaucomatous globe. Dogs were treated postoperatively with topical neomycin/polymyxin B/0.1% dexamethasone and 0.03% flurbiprofen every 6 h tapered over 8-12 weeks, and meloxicam at 0.1 mg/kg orally every 24 h for 7-10 days. IOP, intracameral shunt position and apparent patency, and vision were assessed twice daily for up to 4 (n= 3 eyes) and 10 (n= 2 eyes) days postoperatively, and then at re-examination periods of up to 36 weeks (n= 1 eye). Postoperative complications were recorded and documented photographically. RESULTS: Normal IOP was maintained in all shunted globes (range 10-29 mmHg; mean = 16.7 mmHg at 24 h; IOP = 23 mmHg at 36 weeks) postoperatively for 2 days (3/3 eyes), 8 weeks (2/2 eyes), and 36 weeks (1/1 eye) without additional antiglaucoma therapies. Photopic vision and shunt position and patency were maintained in all shunted globes for all follow-up periods. Postoperative complications included mild aqueous flare and fibrin (n= 3 eyes for 3-10 days postoperatively); intracameral shunt occlusion with fibrin (n= 1 eye at days 2 and 4); partial anterior chamber tube extrusion (n= 1 eye at day 4), and focal corneal edema (n= 1 eye at 18 weeks). Tissue plasminogen activator injected intracamerally through the silicone tube near the frontal sinus effectively resolved the fibrinous shunt occlusion. CONCLUSIONS: The Cullen frontal sinus valved glaucoma shunt shows promise for the management of canine primary glaucoma.     

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.     

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 3 protocols for treatment after induction of remission in dogs with lymphoma

BACKGROUND: The optimal treatment after inducing complete remission (CR) in dogs with lymphoma has not been established. HYPOTHESIS: After inducing CR with L-asparaginase, vincristine, cyclophosphamide, doxorubicin, prednisone (L-CHOP); consolidation with either half-body radiation therapy (HBRT); or lomustine (CCNU) and mechlorethamine, vincristine, procarbazine, prednisone (MOPP) would improve first remission duration compared with continuing a CHOP-based protocol for an additional 4 months. ANIMALS: Dogs with stage III-V lymphoma. METHODS: Prospective clinical trial in which dogs initially were treated with an 8-week induction protocol that consisted of L-CHOP. Dogs in CR after induction were then allocated to 1 of 2 consolidation arms. A chemotherapy consolidation arm consisted of 2 treatments with CCNU and 1 cycle of MOPP. A HBRT arm consisted of 2 sequential 8.0-Gy fractions to the cranial and caudal half-body separated by 30 days. Vincristine was given between fractions. Results of the consolidation arms also were compared with a historical group treated with the same 8-week induction protocol followed by CHOP therapy until week 24. RESULTS: Overall, 67% of the dogs were in CR after 8 weeks of induction chemotherapy and were compared. Fifty-two dogs were in the historical arm, 23 in the CCNU/MOPP arm, and 27 in the HBRT arm. No difference in first remission duration was found among groups. Median first remission duration for the historical, CCNU/MOPP, and HBRT arms were 307, 274, and 209 days, respectively (P = .28). Overall second CR rate was 82% and was not different among groups (all P > or = .58). Overall remission duration (P = .28) and survival time (P = .48) were not different among groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Consolidation with either CCNU/MOPP or HBRT showed no advantage over a standard CHOP-based protocol.     

Surgical treatment and radiation therapy of frontal lobe meningiomas in 7 dogs

The cases of 7 adult dogs with generalized seizures managed by surgical excision and radiation therapy for frontal lobe meningiomas were reviewed. The neurological examination was unremarkable in 6 of the 7 dogs. Five dogs were operated on using a bilateral transfrontal sinus approach and 2 using a unilateral sinotemporal approach to the frontal lobe. One dog was euthanized 14 d after surgery; radiation therapy was initiated 3 wk after surgery in the remaining 6 dogs. Long-term follow-up consisted of neurological examination and magnetic resonance imaging (MRI) and/or computed tomography (CT) scan after radiation therapy. The mean survival time for dogs that had surgery and radiation therapy was 18 mo after surgery. Frontal lobe meningiomas have been associated with poor prognosis. However, the surgical approaches used in these cases, combined with radiation therapy, allow a survival rate for frontal lobe meningiomas similar to that for meningiomas located over the cerebral convexities.     

Primary frontal sinus squamous cell carcinoma in three dogs treated with piroxicam combined with carboplatin or toceranib

In human medicine, primary frontal sinus squamous cell carcinoma (pFS-SCC) is not frequently reported. In veterinary medicine, frontal sinus SCC is exclusively described as an extension of nasal cavity SCC. To our knowledge, this is the first publication concerning canine pFS-SCC, diagnosed using histology or cytology and medical imaging, in three dogs. The tumours extended into the orbit or brain cavity, without nasal involvement. Treatment was initiated with piroxicam-carboplatin. Prolongation of carboplatin delivery with a low dose intensity was performed on dogs with a favourable initial response. Dog 1 achieved a complete remission (CR), but was euthanized 344 days after start of therapy. Dog 2, still alive 3 years after start of therapy and in CR, received 14 carboplatin deliveries. In dog 3, after changing the treatment protocol into piroxicam-toceranib, a significant tumour reduction occurred, but the dog was euthanized after 195 days because of a relapse.     

Anterior chamber to frontal sinus shunt for the diversion of aqueous humor: a pilot study in four normal dogs

Silicone tubing was used to divert aqueous humor from the anterior chamber of the right eye to the rostral compartment of the right frontal sinus in four clinically normal mixed-breed dogs. Biomicroscopic examination, and pneumoapplanation tonometry and tonography, completed for up to 18 weeks postoperatively, confirmed gonioimplant function in all four cases. The dogs were euthanized at 6, 8, 16 and 18 weeks postoperatively. Gonioimplant patency was further confirmed by postmortem examination of the globes, implants and frontal sinuses. Gross and light microscopic examinations revealed iridal attachments to the implant ( n  = 4), mild anterior uveitis ( n  = 3), anterior subcapsular cataracts ( n  = 4), and focal corneal ( n  = 3) and scleral ( n  = 3) scarring in the operated globes. Light microscopic examination of frontal sinus specimens revealed mild lymphocytic proliferation and fibrosis immediately adjacent to the implant entrance site. There were no bacteria detected on aerobic or anaerobic cultures of the frontal sinuses or light microscopic examination of the globes or frontal sinuses. Results indicate that the frontal sinus shunting of aqueous humor is a safe and effective means of extraorbital aqueous diversion with potential applicability in the management of glaucoma.     

Clinical evaluation of 1% cyclosporine for topical treatment of keratoconjunctivitis sicca in dogs.

Keratoconjunctivitis sicca (KCS) is a prevalent and often vision-threatening condition in dogs. In several reports, 2% cyclosporine (cyclosporin A, CsA) was described as effective in modulating the clinical signs of KCS. This study was designed to compare the efficacy of 1% CsA vs a placebo, using a randomized double-blind clinical trial. Topical administration of 1% CsA significantly improved Schirmer wetting values and subjective markers of corneal health as compared with the placebo. In the dogs treated with topical administration of 1% CsA, the clinical signs of KCS were improved in 81.8% of cases.     

A topical aqueous calcineurin inhibitor for the treatment of naturally occurring keratoconjunctivitis sicca in dogs

Purpose The purpose of this study was to evaluate the efficacy of an aqueous calcineurin inhibitor, SCY‐641, in the treatment of naturally occurring canine immune‐mediated keratoconjunctivitis sicca (KCS). Methods A randomized, double‐masked, placebo‐controlled clinical study of 56‐day duration was performed in dogs with naturally occurring immune‐mediated KCS assigned to treatment with either topical twice‐daily aqueous calcineurin inhibitor solution (SCY‐641) or artificial tears (placebo) by the study administrator. Clinical examination and Schirmer tear tests (STT) were performed prior to therapy and at days 7, 14, 28, and 56 after initiation of treatment. Results Twenty dogs were enrolled in the study with ten receiving placebo and 10 receiving SCY‐641 in one or both eyes. No adverse effects were noted with any treatment. There were no significant differences in mean STT values in dogs in group either at day 0 (prior to therapy) or after 7 days of treatment. At 14, 28, and 56 days after initiation of treatment, mean STT and increase in STT over baseline in dogs treated with SCY‐641 were significantly higher than in dogs treated with placebo (P < 0.04). Conclusions SCY‐641 was well tolerated by dogs with naturally occurring KCS, and by 14 days after initiating therapy, dogs treated with SCY‐641 had significantly higher STT than placebo‐treated dogs. These preliminary results indicate that topical SCY‐641, in a stable clear aqueous solution, is efficacious in a spontaneous model of KCS and warrants further evaluation as a treatment of immune‐mediated KCS.     

Distribution and persistence of topical clotrimazole after sinus infusion in normal canine cadavers

Objectives : To determine the in vitro persistence of clotrimazole 1% cream in the canine frontal sinus and to evaluate the distribution of clotrimazole solution over the sino‐nasal mucosa using a previously described surgical treatment protocol for canine nasal aspergillosis. Methods : Two canine skulls were used to monitor the persistence of clotrimazole cream in the lateral frontal sinus at 37°C. The distribution of irrigation solution around the frontal sinus compartments and nasal cavity was determined using six canine cadaver heads by trephining either the lateral or both the lateral and rostral compartments of the frontal sinus. Stain was added to the sinus irrigation solution before visually inspecting the sagittally sectioned heads. Results : Clotrimazole cream persisted in the frontal sinus for at least 96 hours. The nasal cavity mucosa was completely stained in 8 of 12 sides and almost completely stained in the remaining 4 of 12 sides. Flushing irrigation solution through the lateral compartment of the frontal sinus resulted in inadequate staining of the rostral compartment but medicating both the lateral and rostral compartments resulted in complete coating of all frontal sinus mucosa in eight of eight sides. Clinical Significance : Clotrimazole cream has the potential to be retained in the frontal sinus for several days and is distributed effectively in normal canine cadavers. Medicating both the rostral and lateral compartments of the frontal sinus may be indicated in some clinical cases.     

Prognostic factors for radiation treatment of mast cell tumor in 85 dogs

Ninety-five mast cell tumors in 85 dogs were therapeutically irradiated. Median and mean tumor-free times for dogs were 17 and 62.7 months, respectively. Percentages of dogs tumor-free at 1 and 2 years were 78.8 and 77%, respectively. Factors significantly affecting tumor-free time were clinical stage (P less than 0.001) and neoplasm location (P = 0.019). Median and mean survival times were 19 and 61.2 months, respectively. Survival rates at 1 and 2 years were 76.2 and 73.2%, respectively. Prognostic factors that significantly affected survival rates were clinical stage (P less than 0.001), neoplasm grade (P = 0.006), and neoplasm location (P = 0.034). Radiation therapy was an effective treatment of mast cell tumor in dogs.