Introduction

Blastomycosis is a systemic mycotic disease that is identified in cats considerably less commonly than in dogs.^1,2 Most cases of blastomycosis are thought to be caused by Blastomyces dermatitidis; however, in 2013, Blastomyces gilchristii, which is genetically distinct from B dermatitidis, was reported to also be a possible cause.^3,4 Because B dermatitidis and B gilchristii are morphologically and clinically the same, there is no clinical need for genetic sequencing to differentiate the 2 species.^3,4

Blastomycosis results in pyogranulomatous inflammation that typically affects the respiratory system, and transmission is primarily through inhalation.¹ Other less commonly affected tissues in dogs and cats include the regional lymph nodes, skin, eyes, gastrointestinal tract, CNS, and genitourinary system.^5,6,7,8 The organism is endemic in much of the eastern US, specifically in states surrounding the Ohio, Missouri, and Mississippi river valleys; the Great Lakes; and the St Lawrence River.^1,9

Most cats with blastomycosis are young adults,^7,8,10 and a sex predilection among males has been described, as is also the case for dogs.^1,7,10 However, in 1 report,⁸ 6 of 8 cats with blastomycosis were females. Clinical signs in affected cats include pneumonia, dermal lesions, neurologic abnormalities, and ocular abnormalities.^1,7,8,10,11 Nonspecific signs such as lethargy, anorexia, fever, and weight loss are also reported.¹ Peripheral lymphadenopathy does not appear to be a common finding in cats with blastomycosis.⁸ Outdoor exposure is not necessary for infection, as reports^1,7,12,13,14 have described infection in indoor-only cats.

Ocular lesions occur in approximately half of all dogs with blastomycosis,^5,6 with uveitis being the most commonly reported finding in these cases,^5,15,16 and ocular dissemination is believed to start in the choroid.^1,16 Publications describing ocular lesions in cats with blastomycosis are limited to case reports and small case series,^7,8,17,18 although 2 reviews^7,10 reported that ocular involvement occurs in 26% to 38% of affected cats. Reported abnormalities include blindness, anterior uveitis, chorioretinitis, retinal granulomas, and retinal detachment.^7,8,17,18 Additionally, CNS involvement has been described in 30% to 41% of cats.^7,8,10 Signs include ataxia, paresis, circling, and head tilt. Neuro-ophthalmic abnormalities such as Horner syndrome, anisocoria, and an absent menace response may reportedly also occur,^7,8,19 and CNS infection may occur without evidence of active systemic dissemination.¹⁹ Serum biochemical and hematologic abnormalities are nonspecific and may include an inflammatory leukogram.⁸ Hypercalcemia has been reported in cats with blastomycosis.^8,20 The prognosis for cats with treatment is considered good; however, cats with CNS disease have a worse prognosis.¹

Because blastomycosis is diagnosed much less frequently in cats than dogs, even in areas where the organism is endemic, veterinarians should be aware of the types of clinical abnormalities that can typically occur in affected cats. The objective of the study reported here was to document ocular findings in cats with confirmed blastomycosis examined at the University of Tennessee between 1978 and 2019.

Materials and Methods

Results

Blastomycosis was confirmed in 35 cats during the study period. Mean age of the 33 cats for which age was known was 6.8 years (SD, 4.7 years; range, 1 to 16 years). There were 33 domestic shorthair cats and 2 Siamese cats. Nineteen (54%) were males (18 neutered and 1 sexually intact), and 16 (46%) were females (14 neutered and 2 sexually intact). Six cats were reported to be indoor-only cats, and 4 were reported to be indoor-outdoor cats; no notations were made for the remaining cats.

Twenty-two cats were confirmed positive for blastomycosis by means of cytologic identification of Blastomyces organisms in aspirates from skin lesions (n = 9), lung (4), lymph nodes (3), subconjunctival masses (2), nasal masses (2), aqueous humor (1), or liver (1). Four cats were confirmed positive for blastomycosis by means of antemortem culture of aqueous humor, skin lesions, transtracheal wash fluid, or tissue obtained via craniotomy. Four additional cats were confirmed positive for blastomycosis by means of antemortem histologic examination. Eleven cats underwent necropsy, and blastomycosis was confirmed in all 11. Six cats had confirmation of the diagnosis by means of multiple diagnostic modalities. Six cats were tested with a quantitative urine enzyme immunoassay, and results were positive for 5 of the 6. In 4 cats, an agar gel immunodiffusion assay was performed, and results were initially negative in all 4. One cat subsequently seroconverted after 2 months of treatment with itraconazole; the other 3 cats were not retested. One cat had negative results for both the urine enzyme immunoassay and agar gel immunodiffusion assay but was confirmed to have blastomycosis by means of cytologic examination of nasal samples and appeared to have only localized disease.

Clinical findings

Of the 35 cats, 18 were examined by a board-certified veterinary ophthalmologist or veterinary ophthalmology resident, 14 underwent a light examination of the anterior segment and fundus by veterinary internist or neurologist or veterinary internal medicine or neurology resident, and 3 did not undergo an antemortem ocular examination (only 1 of the 3 had the eyes examined histologically). Twenty-one of the 35 (60%) cats had evidence of ocular abnormalities. The 14 cats that did not have ocular lesions had other abnormalities, including skin lesions (n = 6), dyspnea (6), fever (1), emaciation (1), an axillary mass (1), and nasal discharge (1), and were not included in further analyses. Two of the 21 cats with ocular lesions had bullous retinal detachments and concurrent systemic hypertension, and signs in both cats resolved with itraconazole and treatment for hypertension. Because the ocular lesions could have been secondary to either hypertension or blastomycosis, these 2 cats were excluded from further analyses.

Of the remaining 19 cats, 15 (79%) had bilateral ocular signs. Ten of the 19 (53%) cats had inflammatory lesions, and 9 (47%) had neuro-ophthalmic abnormalities. Nine of the 19 (47%) cats were presented for evaluation of ocular signs; the others were presented for evaluation of systemic signs.

Of the 10 cats with inflammatory ocular lesions, 5 were affected bilaterally, and 5 were affected unilaterally at presentation. Clinically, 7 eyes had anterior uveitis manifesting as aqueous flare (n = 5 eyes), hypopyon (2), hyphema (2), uveal granulomas (2), keratic precipitates (1), or fibrin deposits (1); 6 eyes had posterior segment inflammation manifesting as active chorioretinitis (6), retinal detachment (4), vitritis (1), retinal hemorrhage (1), or perivascular cuffing (1); and 2 eyes had panuveitis. Three eyes had secondary glaucoma, including 2 eyes with panuveitis identified clinically and 1 eye with anterior uveitis identified clinically with panuveitis diagnosed histologically. Other abnormalities consisted of corneal ulceration (n = 3 eyes), secondary glaucoma (3), chemosis (2), conjunctivitis (2), buphthalmia (1), a subconjunctival mass (1), and an orbital mass (1; Figures 1 and 2).

View Full Size

Photograph of the eye of a 2-year-old domestic shorthair cat with blastomycosis showing hypopyon and hyphema. Image published with the permission of the University of Tennessee College of Veterinary Medicine, the copyright holder; all rights reserved. Individuals wishing to reproduce the image should contact Diane Hendrix, UTCVM, 2407 River Dr, Knoxville, TN 37996.

Citation: Journal of the American Veterinary Medical Association 260, 4; 10.2460/javma.21.03.0135

• Download Figure
• Download figure as PowerPoint slide

View Full Size

Photograph of the eye of an 8-year-old domestic shorthair cat with blastomycosis. Notice the conjunctival hyperemia and conjunctival billowing secondary to subconjunctival and orbital pyogranulomatous inflammation; Blastomyces organisms were present. The cornea is edematous with ulceration and vascularization. Image published with the permission of the University of Tennessee College of Veterinary Medicine, the copyright holder; all rights reserved. Individuals wishing to reproduce the image should contact Diane Hendrix, UTCVM, 2407 River Dr, Knoxville, TN 37996.

Citation: Journal of the American Veterinary Medical Association 260, 4; 10.2460/javma.21.03.0135

• Download Figure
• Download figure as PowerPoint slide

Presenting complaints for the 9 cats with neuro-ophthalmic abnormalities consisted of seizures (n = 4 cats), circling (3), recumbency (1), and extensor rigidity (1). Fifteen of the 18 eyes were abnormal on ophthalmic examination. Seven of 9 cats were affected bilaterally, 1 cat had unilateral involvement, and 1 cat had histologic changes on necropsy that were not seen on examination. The most common abnormality group was blindness with normal pupillary light responses (assessed by an absent menace response or lack of ocular tracking), which was bilateral in 4 cats and unilateral in 2 cats (ie, 10 eyes). One cat had negative pupillary light responses and an absent menace response in both eyes, and 1 cat had negative pupillary light responses and an absent menace response in both eyes but was positive for tracking. One cat with dull mentation had bilateral superficial linear corneal ulcers. Other abnormalities included anisocoria (n = 2 cats), nystagmus (2), and Horner syndrome (1).

Thoracic radiographs were available for 15 of the 19 cats with ophthalmic abnormalities, and 12 of the 15 (80%) had abnormalities. The most common radiographic finding was a structured interstitial pattern suggestive of pulmonary nodules (n = 7 cats); other abnormalities were cavitary pulmonary lesions (2), pleural effusion (3), and unstructured interstitial pulmonary patterns (3).

Two cats with inflammatory ocular lesions underwent diagnostic imaging. Magnetic resonance imaging of 1 cat with conjunctival thickening and uveitis of the right eye and negative pupillary light and menace responses in the left eye had marked infiltration of the left optic nerve and chiasm seen on MRI images. The right eye had retinal detachment and thickening of the sclera and optic nerve that were not appreciated on ophthalmic examination. Additionally, a 1-cm mass in the region of the optic chiasm caused caudodorsal deviation of the thalamus. Computed tomography of a cat with exophthalmia showed marked soft tissue swelling in the orbit and retinal detachment. Only 2 cats with neuro-ophthalmic abnormalities underwent advanced diagnostic imaging. Computed tomography showed a contrast-enhancing mass in the right cerebrum of 1 cat, and MRI showed a suspect granuloma in the right cerebrum of the other.

Six of the 10 cats with inflammatory ocular lesions underwent histologic examination of the globes: 2 cats underwent histologic examination of enucleated globes, and 4 cats underwent examination of the globes at necropsy. Three cats had pyogranulomatous, 2 had granulomatous, and 1 had neutrophilic inflammation with intralesional yeast organisms. Ocular tissues affected included the extraocular muscles, sclera, anterior chamber, ciliary body, retina, choroid, and optic nerve. One eye had lymphocytic endophthalmitis with no yeast identified. This eye had been enucleated 7 months after the diagnosis of blastomycosis because it had become phthisical after treatment with itraconazole. In the 4 cats with inflammatory lesions that underwent necropsy, Blastomyces organisms were identified in the integument (n = 2), lymphatic (2) and pulmonary (3) systems, and CNS (3). Three cats had pyogranulomatous meningoencephalitis diagnosed on necropsy. Two of these 3 cats were clinically blind but did not have ocular lesions commensurate with blindness and had no other neurologic signs. The third cat had been presented because of dyspnea, had iris granulomas, was visual on clinical examination, and had no neurologic signs.

Nine cats had neuro-ophthalmic abnormalities; 6 underwent necropsy. CNS abnormalities included pyogranulomatous or granulomatous meningoencephalitis (n = 4), suppurative encephalitis (1), and pyogranulomatous focal myelitis with encephalitis (1). Eyes were examined histologically from 3 of the 6 cats with neuro-ophthalmic signs that underwent necropsy; 1 had pyogranulomatous choroiditis with intralesional yeast organisms that was not observed antemortem, while the other 2 were normal. Nonocular and non-CNS tissues with inflammation secondary to Blastomyces infection included pulmonary (4), lymphatic (2), otic (1; otitis media and interna), and integumentary (1) tissues. Organisms were present in all areas of inflammation.

Eleven of the 19 cats died or were euthanized prior to or soon after the diagnosis of blastomycosis or shortly following initiation of treatment. Three cats were lost to follow-up after receiving no treatment, treatment with itraconazole, or treatment with amphotericin B. Four cats received long-term antifungal treatment, with 3 cats treated with itraconazole alone for 3, 7, and 8 months. Eyes with anterior uveitis were treated with ophthalmic prednisolone acetate and ophthalmic atropine when indicated. Two cats had resolution of all clinical signs and remained visual. One cat had resolution of nonocular signs, but the affected eye was enucleated because of phthisis bulbi. One cat was initially treated with fluconazole, and after 3 months of treatment, the cat was switched to itraconazole. All systemic clinical signs resolved except that the affected eye had developed secondary glaucoma and was enucleated. One cat with neurologic signs responded to itraconazole and fluconazole with resolution of neurologic signs and blindness, but 2 months later, the cat developed lymphosarcoma and was euthanized.

Discussion

In the present study, 21 of 35 (60%) cats examined between 1978 and 2019 because of systemic blastomycosis had an associated ocular abnormality. After elimination of 2 cats with systemic hypertension in addition to ocular abnormalities, 10 of 19 (53%) cats had inflammatory lesions, such as anterior uveitis and chorioretinitis, typically associated with systemic fungal infections, and 9 (43%) had ocular manifestations of CNS disease, including cortical blindness, absent pupillary light responses, anisocoria, and Horner syndrome. Findings in this larger study corroborated those reported in previous literature reviews and smaller case studies.^7,8,10

Ocular lesions in the cats in the present study were similar to those reported for dogs, with uveitis (anterior uveitis, posterior uveitis, and panuveitis) being most common.^{5,7,8,10,15,16} Clinical findings for dogs and cats with ocular blastomycosis reflect severe inflammation affecting nearly all components of the globe. Specific clinical signs in dogs include blindness, anterior uveitis, keratitis, corneal edema, conjunctivitis, scleral staphylomas, periorbital granulomas, cataract formation, lens rupture, vitreal hemorrhage, vitritis, chorioretinitis, optic neuritis, retinal detachment, retinal granulomas, panophthalmitis, and secondary glaucoma.^5,15,16,22 Ocular involvement is reported to occur in 40% to 50% of dogs with blastomycosis.^5,6

Findings of our study were generally consistent with previously reported inflammatory ocular signs caused by blastomycosis. The most common finding was anterior uveitis, followed by posterior segment inflammation and panuveitis. Additionally, 2 cats in this study had thickened conjunctiva causing a mass effect, and 1 had orbital disease. Cytologic examination of fine needle aspirates of these conjunctival masses revealed yeast organisms.

The prognosis for vision in dogs with ocular blastomycosis varies with the extent of ocular disease. Dogs with posterior segment disease alone tend to respond better to treatment than those with anterior uveitis or panophthalmitis.^15,23 Secondary glaucoma occurs in 26% to 41% of dogs with ocular blastomycosis and is a common reason for enucleation.^15,24 Secondary glaucoma was diagnosed in only 2 of the 10 cats with inflammatory ocular lesion in the present study, both of which had panuveitis. Thus, the incidence of secondary glaucoma in cats with blastomycosis may be lower than that in dogs; however, the low incidence of secondary glaucoma in the present study may also have been due to the fact that long-term follow-up was available for very few treated cats in this population. The present study had only 4 cats (5 affected eyes) with inflammatory ocular changes that received long-term treatment; therefore, the prognosis for vision and likelihood of secondary glaucoma are hard to determine. However, 2 of the 5 eyes had panophthalmitis and were enucleated. One eye with anterior uveitis and 2 eyes with chorioretinitis remained visual.

Blastomycosis is endemic in Tennessee, and over the study period, blastomycosis was diagnosed in approximately 900 dogs at the University of Tennessee. Over that same time period, 5 times as many dogs were seen as cats. Even so, blastomycosis is far less commonly diagnosed in cats. The present study did not identify a clear age or sex predilection for cats with blastomycosis. Ages ranged from 1 to 16 years (mean, 6.8 years), and the proportions of male (19/35 [54%]) and female (16/35 [46%]) cats were approximately equal. Previously, an age predilection for young to middle-aged cats and a sex predilection for male cats have been reported.^1,7,8,10 Young, male, large-breed dogs are most commonly affected with blastomycosis.^5,6,16

To our knowledge, there are no studies evaluating the sensitivity and specificity of diagnostic tests for the diagnosis of blastomycosis in cats. In dogs, the Blastomyces quantitative urine antigen enzyme immunoassay is a diagnostic tool with useful clinical application. It is a highly sensitive test,^25,26 but cross-reactivity with multiple fungal antigens substantially decreases its specificity.^21,25,26 The enzyme immunoassay has been reported to be 76% to 100% sensitive for identification of blastomycosis in dogs with the disease.^27,28 Diagnosis of blastomycosis in dogs with antibody detection via an agar gel immunodiffusion assay is considerably less specific with variable specificity.^1,28,29 Five cats with generalized disease in the present study that underwent testing with the enzyme immunoassay had positive results, but 4 of these 5 cats tested with the agar gel immunodiffusion assay had false negative findings, reflecting the test’s low sensitivity previously reported in dogs.

Microscopic evaluation of ocular blastomycosis in both cats^1,7,17,18 and dogs^5,22 shows evidence of purulent to pyogranulomatous inflammation with yeast organisms located primarily in the choroid. Rarely, yeast organisms are seen in the retina and anterior segment of dogs.^5,22 The inflammatory responses seen in the present study were similar to those previously reported for dogs. All eyes that had active disease had Blastomyces organisms present, with most of the organisms in the posterior segment. Organisms were also identified in the optic nerve, extraocular muscles, and sclera, emphasizing the generalized effect that blastomycosis has on the eye in dogs and cats.

Nine of the 35 cats with confirmed blastomycosis (26%) in this study had CNS disease, with the most common diagnosis being pyogranulomatous meningoencephalitis. This contrasts with dogs, with neurologic signs reportedly occurring in < 5% of dogs with blastomycosis.³⁰ Signs in dogs are most commonly associated with intracranial extension of a mass from the nasal cavity, ventriculitis, or a solitary CNS granuloma.³¹ Signs include depression, seizures, and neurologic deficits such as circling, ataxia, blindness, abnormal pupillary light responses, and nystagmus.^1,30 In contrast, none of the cats in the present study had ventriculitis or extension of disease from the nasal cavity into the brain. Neurologic signs in this population and those previously reported include ataxia, paresis, circling, and head tilt. Neuro-ophthalmic abnormalities such as Horner syndrome, anisocoria, and an absent menace response were also noted in this population, as well as previously.¹⁹ None of the cats without ocular abnormalities in the present study had neurologic signs.

Unlike dogs, peripheral lymphadenopathy is not a commonly reported finding in cats with blastomycosis.⁸ In our study, the diagnosis of blastomycosis was confirmed in 3 of the 35 cats through cytologic examination of peripheral lymph node aspirates. When blastomycosis is suspected and regional lymphadenopathy is present, sampling of these tissues may be a useful diagnostic tool in cats as it is in dogs.

The present study had several limitations. Because the study was conducted at a university teaching hospital, most of the cases had severe disease at presentation, and the true prevalence of ocular involvement in cats with blastomycosis and its prognosis may vary in a different practice setting from what was found in this study. Additionally, because this study was retrospective, there may have been deficiencies or inconsistencies in the medical records. Some of the cases included in this study were seen > 40 years ago. It is reasonable to deduce that disseminated blastomycosis would be associated with a lower mortality rate today owing to greater knowledge of the disease, use of the urine antigen enzyme immunoassay allowing for earlier diagnosis, and the availability of itraconazole and fluconazole.

There were also limitations regarding the ocular examinations. A fundic examination could not be completed in 3 eyes owing to severe disease in the anterior chamber. Additionally, not all affected eyes underwent histologic examination. Therefore, the true prevalence of posterior lesions may be underrepresented. A menace response is not a reliable method of testing vision, especially in cats. Although determination of a cat’s visual status via a menace response can be difficult, the clinical diagnosis of blindness was corroborated in all cats in this study via necropsy or advanced imaging and the relationship of each lesion’s location to the clinical signs. Even though several of the cats with neuro-ophthalmic abnormalities presented for seizure activity, the negative menace response was not thought to be attributable to a postictal state. None of the cats recovered a menace response, and none were known to have recently had a seizure. Finally, 1 cat included in the present study was previously reported by Smith et al.¹⁹ Five other cats in this study may have been previously reported by Breider et al¹¹; however, because of the way the signalment was reported in that study, it is impossible to know.

In most cases, complete neurologic and ophthalmic examinations, in combination with thoracic radiography and cytology, were sufficient for diagnosis. In most of the neurologically affected cats, the diagnosis was made on the basis of clinical signs and aspiration of pulmonary nodules or lymph nodes, and CT or MRI was not required. Other cases were so advanced at the time of presentation that euthanasia and necropsy were elected.

Blastomycosis has long been considered the primary differential diagnosis for dogs with uveitis or panuveitis in areas where the organism is endemic. The spectrum of inflammatory ocular disease seen in the cats in the present study, except for possibly a greater prevalence of conjunctival disease, was similar to that in dogs. But, given the findings of this study, blastomycosis should also be considered a differential diagnosis for cats with CNS disease that may only be evident as pupillary or vision abnormalities. Although the ocular abnormalities are similar, neurologic abnormalities were more common in these cats, compared with previous reports of dogs. The diagnosis can be made in many ways, but visualization of the organism through histopathology, culture, or cytology is the gold standard. Additional research is needed to determine the sensitivity and specificity of the urine antigen enzyme immunoassay in cats, and information on long-term outcomes for cats with blastomycosis treated with itraconazole, fluconazole, or amphotericin B is lacking, even in this case series, so additional study is needed in this area as well.