Clinical aspects of natural infection with Blastomyces dermatitidis in cats: 8 cases (1991–2005)

Chen Gilor Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802.

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Thomas K. Graves Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802.

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Anne M. Barger Department of Pathobiology, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802.

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Kristen O'Dell-Anderson Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802.

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Abstract

Objective—To evaluate clinical and laboratory findings, treatment, and clinical outcome in cats with blastomycosis.

Design—Retrospective case series.

Animals—8 cats with naturally occurring blastomycosis.

Procedures—Medical records of the University of Illinois Veterinary Teaching Hospital were searched for cases of blastomycosis in cats diagnosed via cytologic or histopathologic findings. Clinical and laboratory findings, treatment, and clinical outcome were determined. Radiographs were reviewed for the 8 cases.

Results—All cats were systemically ill. Respiratory tract signs and dermal lesions were most commonly observed. All cats had radiographic evidence of respiratory tract disease. Seven of the 8 cats had ill-defined soft-tissue opacities (nodules or masses) or alveolar consolidation of the lungs. Antemortem diagnosis was achieved cytologically in 6 of the 8 cats, and 3 were successfully treated and survived.

Conclusions and Clinical Relevance—In contrast to previous reports, diagnosis was achieved antemortem in most of the cats (all by cytologic identification of the organism). Clinical signs, laboratory findings, and outcome were similar to previous descriptions of this rare disease in cats.

Abstract

Objective—To evaluate clinical and laboratory findings, treatment, and clinical outcome in cats with blastomycosis.

Design—Retrospective case series.

Animals—8 cats with naturally occurring blastomycosis.

Procedures—Medical records of the University of Illinois Veterinary Teaching Hospital were searched for cases of blastomycosis in cats diagnosed via cytologic or histopathologic findings. Clinical and laboratory findings, treatment, and clinical outcome were determined. Radiographs were reviewed for the 8 cases.

Results—All cats were systemically ill. Respiratory tract signs and dermal lesions were most commonly observed. All cats had radiographic evidence of respiratory tract disease. Seven of the 8 cats had ill-defined soft-tissue opacities (nodules or masses) or alveolar consolidation of the lungs. Antemortem diagnosis was achieved cytologically in 6 of the 8 cats, and 3 were successfully treated and survived.

Conclusions and Clinical Relevance—In contrast to previous reports, diagnosis was achieved antemortem in most of the cats (all by cytologic identification of the organism). Clinical signs, laboratory findings, and outcome were similar to previous descriptions of this rare disease in cats.

Blastomycosis is a systemic mycotic infection caused by the dimorphic fungus Blastomyces dermatitidis, which, in tissues, is an asexually replicating yeast characterized by round, 5- to 20-mm-diameter, broad-based structures with a thick, refractile, double-contoured cell wall.1 The organism causes a systemic pyogranulomatous disease process most commonly reported in dogs2 and humans3 and infrequently reported in cats4,5 and a variety of many other species such as nondomesticated felids,6 horses,7 dolphins,8 and bats.9 Blastomycosis has been reported worldwide.10 In North America, its endemicity has a well-defined geographic distribution that includes the state of Illinois. Even within regions of endemicity, however, B dermatitidis is found in geographically restricted foci of moist, acidic soil enrichedwith decaying vegetation or animal excreta.11,12 The reservoir for the organism is thought to be soil, where it grows in a saprophytic mycelial form. Living near a lake, a river, or a stream is a risk factor for infection in dogs,12–14 but the disease has been reported in cats that live strictly indoors.4

Although case reports of blastomycosis in cats exist,15–24 they seem to be conflicting in regards to age and breed predisposition. To our knowledge, all reported cases are included in 2 reviews published in 19904 and 1996.5 Immunosuppression does not seem to play a role in predisposition to the disease.1 Infection in cats is reported to occur primarily by inhalation of aerosols containing infective spores. The spores enter the terminal airways and establish a primary infection in the lungs. From there, the yeast can disseminate via the blood or lymphatic system to other organs.1 As reported, affected organs include lungs, CNS, eyes, and skin. Systemic signs of illness such as anorexia, lethargy, and weight loss are commonly reported.4,5

Most feline cases reported in the literature were diagnosed only at necropsy.3,4,16,20–24 The organism was readily identified in histopathologic sections of affected tissues and occasionally in aspirates. Serologic examination was used uncommonly and rarely yielded positive results.4,5 Reports regarding the response to treatment are rare and are confounded by the low rate of antemortem diagnosis and the lack of azoles at the time of diagnosis, which are currently recommended for treatment. In dogs, itraconazole is typically recommended at a dose of 5 mg/kg (2.3 mg/lb), every 12 to 24 hours.2

The purpose of the study reported here was to evaluate clinical and laboratory findings, treatment, and clinical outcome in cats with blastomycosis.

Criteria for Selection of Cases

The University of Illinois medical records database was searched for records of cats with blastomycosis diagnosed between 1991 and 2005. Only records with cytologic or histopathologic confirmation of the diagnosis were included.

Procedures

Results of full history and physical examinations, CBCs, serum biochemical profiles, and thoracic radiography were recorded in all cases. Signalment, month of diagnosis, retrovirus status and concurrent diseases, clinical signs, laboratory results, method of diagnosis, and outcome were determined.

Results

Eight cases of feline blastomycosis were diagnosed between 1991 and 2005. Six cats were spayed females, and 2 were neutered males. Mean age at time of diagnosis was 7.8 years (range, 2 to 13 years). Seven cats were older than 7 years. Seven cats were domestic shorthair, and 1 was a domestic longhair. Five were reported to be indoor-outdoor cats, and 1 was an indoor-only cat; the status of the remaining 2 was unknown. The duration of clinical signs prior to diagnosis ranged from 3 to 30 days. Diagnosis was made during January (n = 1), February (2), April (1), July (2), and October (2). Seven cats had been treated by referring veterinarians with antimicrobials and 6 with glucocorticosteroids. All cats had negative test results for FIV and FeLV infection, as reported by referring veterinarians. In 1 cat, diabetes mellitus had been diagnosed months before and the cat was being treated with insulin at the time of evaluation. No other concurrent diseases were detected. Six cats were referred with chief complaints of respiratory tract disease, 1 was referred for neurologic signs, and 1 for skin disease.

All cats had systemic signs of illness, which included decreased appetite (n = 7), fever (6), weight loss (6), and lethargy or signs of depression (6). Dehydration was detected in only 2 cats at initial evaluation.

Respiratory tract signs were evident in 6 of the 8 cats, including increased bronchovesicular sounds (n = 4), dyspnea (4), tachypnea (3), coughing (3), and sneezing (1).

Skin lesions were evident in 7 cats. Five had 1 or more nonulcerated dermal masses ranging from a few millimeters to a few centimeters in diameter. These masses were on the head or eyelid, inside the pinnae, or on the trunk. One of the 5 cats (the diabetic cat) also had draining tracts. The masses and draining tracts were evaluated cytologically in 4 cats, and blastomycosis was confirmed. Two cats had alopecia and erythema, which were not specifically attributed to blastomycosis. None of the 8 cats had pruritus, and none had peripheral lymphadenomegaly.

Ocular signs were evident in 3 cats, and 2 of these cats also had CNS signs. One cat had bilateral ocular signs, and fundic examination revealed retinal lesions consistent with fungal granulomas and retinal detachment. The second cat had bilateral retinal granulomas without detachment and neurologic signs (head tilt and signs of pain in the thoracolumbar portion of the vertebral column). The third cat had unilateral ocular signs (uveitis, retinal granulomas, and retinal detachment) and bilateral hind limb paresis. Histopathologic findings in this cat included anterior uveitis, posterior chorioretinitis, and multifocal encephalitis and myelitis. In addition to these 3 cats, a fourth cat had Horner syndrome as well as chronic retinal degeneration in the right eye. At necropsy, no evidence of blastomycosis was found in the eyes or CNS of this cat. This cat did have a mediastinal fungal granuloma that could have been the cause of Horner syndrome.

Results of CBCs were nonspecific. Lymphopenia was observed in 4 cats that had lymphocyte counts ranging from 0.34 × 103 cells/μL to 1.1 × 103 cells/μL (reference range, 1.7 × 103 cells/μL to 7.0 × 103 cells/μL). All 4 received glucocorticoids prior to evaluation at our hospital. Leukopenia with a WBC count of 2.85 × 103 cells/μL (reference range, 5.5 × 103 cells/μL to 19.5 × 103 cells/μL) and basophilic neutrophils were evident in 1 cat. One cat had mild normocytic normochromic anemia, with an Hct of 24.5% (reference range, 30% to 45%). Serum biochemical results were also nonspecific. Four cats had high serum total protein concentrations ranging from 8.2 to 9.2 g/dL (reference range, 5.8 to 8.0 g/dL). Only in 1 cat was this finding attributed to clinically apparent dehydration (albumin and globulin concentrations were both high). One cat had high serum globulin concentration. The other 2 cats had concentrations of albumin and globulin in the upper portion of the reference range, resulting in slightly high total protein concentration. One cat had high serum globulin concentration (5.3 g/dL) with concurrent hypoalbuminemia (2.3 g/dL; reference range, 2.7 to 3.8 g/dL) and serum total protein concentration within reference range. Serum glucose concentrations were slightly high in 5 cats, ranging from 150 to 192 mg/dL (reference range, 65 to 129 mg/dL), and could have been related to stress or glucocorticosteroid administration, although 1 cat had concurrent diabetes mellitus. Two cats had high serum total calcium concentrations of 12.2 and 12.6 mg/dL (reference range, 8.4 to 10.8 mg/dL). Serum ionized calcium concentration was not measured in any of the cats. Urinalysis was performed in 4 cats, and results were within reference ranges, except for 1 cat with RBCs in the urine (attributed to cystocentesis) and 1 cat with glucosuria that had concurrent diabetes mellitus. Serologic tests for anti-Blastomyces antibodies were not performed in any of the cats.

All cats, including the 2 without clinical signs of respiratory tract disease, had radiographic signs of respiratory tract disease. Seven of the 8 cats had poorly defined soft tissue opacities consistent with nodules or masses or alveolar consolidation of the lungs. The right cranial lung lobe was commonly involved (n = 5 cats). Radiographic evidence of pleural effusion was identified in the eighth cat. Four cats had diffuse bronchial lung patterns. Diffuse miliary soft tissue opacity nodules (n = 3 cats), a cranial mediastinal mass (n = 1), and perihilar lymphadenomegaly (3) were also reported. Ultrasonographic examination of the thorax was performed in 1 cat, and findings included a homogeneous, hypoechoic, and consolidated left caudal lung lobe and a cavitated nodule in the right caudal lung lobe.

Diagnosis of blastomycosis was achieved antemortem by use of cytologic examination in 6 cats and postmortem in 2 cats. Microscopically, via cytologic or histologic examination or both, double-walled yeast of the appropriate size with broad-based budding were easily identified in all cats and were surrounded by pyogranulomatous inflammation. In 4 cats, cytologic examination was done on samples collected via fineneedle aspiration (in 1 cat from dermal lesions, in 2 cats from dermal lesions and lungs, and in 1 cat from spleen). In another cat, a diagnostic cytologic sample was collected from the skin by use of an impression smear from an exudative draining tract rather than by fine-needle aspiration. Cytology of a bronchoalveolar lavage sample was diagnostic in the remaining cat.

Blastomycosis was diagnosed in 2 cats postmortem via histologic examination after a complete necropsy examination. In 1 cat, only the lungs and tracheobronchial lymph nodes were affected. Antemortem diagnosis had been attempted in this cat by collection of pleural fluid. Fluid analysis revealed a modified transudate (total protein, 4.5g/dL; nucleated cells, 7.7 × 103 cells/μL) with neutrophils as the predominant cells but with no organisms. In the other cat, lesions were identified in the lungs, eyes, brain, spinal cord, spleen, trachea, tracheobronchial lymph nodes, liver, kidneys, and heart. Pericardial, pleural, and peritoneal effusions were also found in this cat.

Combining the clinical, laboratory, and postmortem findings revealed that all cats in this study had blastomycosis involving the lungs. Two cats had lung disease only. Five cats had dermal lesions caused by blastomycosis. In 3 cats, more than 2 organs were involved, including lungs, skin, eyes, brain, and spinal cord. Other affected organs were spleen, trachea, tracheobronchial lymph nodes, liver, kidneys, and heart. Pericardial, pleural, and peritoneal effusions were also found.

Four cats were euthanized because of respiratory failure: 2 before diagnosis and 2 within 2 days after diagnosis and despite treatment. Of the 2 that were treated and did not survive, 1 was evaluated for dyspnea and had a severe diffuse bronchial lung pattern radiographically. There was no clinical evidence of disease of other organ systems in this cat. Treatment with itraconazole was initiated, but the cat was euthanized shortly thereafter because of respiratory failure, and a necropsy was not performed. The other cat was evaluated for hind limb paresis and had ocular lesions. This cat was treated with fluconazole but was also euthanized because of respiratory failure before a response to treatment was observed. Four cats were treated and sent home; 3 were prescribed itraconazole (7.3 mg/kg [3.3 mg/lb], q 24 h; 5 mg/kg [2.3 mg/lb], q 12 h; or 8 mg/kg [3.6 mg/lb], q 12 h; PO). One cat with CNS and ocular disease was treated with fluconazole at 5 mg/kg, PO, every 12 hours. Of the 4 cats that were sent home, 1 was lost to follow-up. The other 3 were treated for 3 to 5 months, and their infections resolved. Clinical improvement was seen within 1 week after initiating treatment, but radiographic evidence of lung disease was still evident at 3 months and was gone at 5 months. The cat with diabetes mellitus died from diabetes-related complications after 8 months. The cat treated with fluconazole was lost to follow-up after 1 year. The third cat did not have complete resolution of clinical signs. At initial evaluation, the cat had retinal granulomas and detachment and was treated with itraconazole; after 4 months of treatment, the cat had subretinal hemorrhage and was blind. It is still blind, but apparently free of infection 5 years later.

Discussion

Blastomycosis is reported rarely in cats. To the authors' knowledge, this retrospective case series of 8 cases diagnosed at the University of Illinois Veterinary Teaching Hospital during 14 years is the largest case series from a single hospital. Two literature reviews4,5 have been published. In the first review, there were 3 new cases and 20 cases reviewed from the literature.4 In the other, data were compiled from 2 sources: published case reports (22 cases, mostly reported in the first review) and data from 19 cases in the Veterinary Medical Data Base.5 The Veterinary Medical Data Base cases were incomplete and included only signalment, geographic location, season of diagnosis, and concurrent diseases. In agreement with the authors,5 we believe the results may have been skewed by overlap of cases from the 2 sources. To our knowledge, no other studies on blastomycosis in domestic cats have been published. Lack of uniformity of data and possible case duplication made evaluation of the disease difficult in previous studies.4,5

The study reported here also had limitations. The number of cases was small and did not necessarily represent the prevalence of the disease accurately. Because cats in the study were referred to a university teaching hospital, the complexity and severity of the clinical findings might have been exaggerated.

Previous reports regarding signalment of cats with blastomycosis were inconsistent. Whereas in 1 study,4 75% of cats were < 4 years old (mean age was not reported), in the other study,5 only 42% were < 4 years old and mean age was 5.9 years. In the study reported here, mean age was 7.8 years (range, 2 to 13 years) and 7 of 8 cats were > 7 years of age. Age at time of diagnosis ranges in the literature from 6 months to 18 years.4 In contrast, diagnosis in dogs is typically made at an early age (2 to 4 years13). Diagnosis of blastomycosis was more common in male cats in previous reports,4 in contrast to the present report of 6 females and only 2 males. The reported predisposition of Siamese,4 Abyssinian,5 and Havana Brown cats5 was not supported by our findings. When data from the present study were combined with the review by Davies and Troy,5 61% of cats were male, mean age was 6.5 years, and only 32% were < 4 years of age. As reported elsewhere, blastomycosis can occur in cats that live strictly indoors4 and there is no apparent season associated with the disease.4,5 All cats in the present study had negative test results for FIV antibodies and FeLV antigen, and there was no apparent immunosuppression that might have predisposed them to develop the disease. One cat may have been immunocompromised by diabetes mellitus, but that cat was treated successfully and recovered from blastomycosis. In a previous study,5 4 of 41 cats had positive results for FeLV antigen, 1 had feline infectious peritonitis, and no other concurrent diseases were reported. Decreased cell-mediated immunity and lymphopenia have been associated with blastomycosis in dogs.25 Lymphopenia has been rarely reported in cats with blastomycosis4 but was detected in 4 of the 8 cats in the present study; whether this was a contributing factor or secondary to infection, stress, or previous administration of glucocorticoids was not determined. A stress leukogram, however, including neutrophilia and lymphopenia, was detected in only 1 cat in this study.

The clinical signs reported here are largely consistent with previous reports, although fever was commonly detected in the present study (6/8 cats) and was reported rarely in previous studies.4,5 Systemic signs of decreased appetite (7/8 cats), lethargy (6/8), and weight loss (6/8) were also more common than reported by Davies and Troy5 (54% in total). The frequency of respiratory tract signs was similar in this report and the report by Davies and Troy.5 Respiratory tract signs may not be an accurate indicator of the actual degree of involvement of the respiratory system in the systemic infection. All cats in the present study had radiographic evidence of respiratory tract involvement, whereas 2 had no clinical signs of respiratory tract disease. All 3 cats in which necropsy was performed had histopathologic evidence of respiratory tract disease. A final diagnosis of respiratory tract disease on necropsy in the Davies and Troy5 report was not as common (59%), although in the 8 cats that were examined via thoracic radiography, 6 had radiographic evidence of disease.

Ocular and CNS involvement have been reported in approximately 30% to 32% and 18% to 26% of affected cats, respectively,4,5 which is similar to the prevalence of disseminated disease in those studies (32%). In the present study, CNS and ocular disease were detected only in association with disseminated disease and were detected in 3 of 8 cats. Dermal masses were detected in 5 of 8 cats, in contrast to only 9%4 and 30%5 in previous studies. This marked difference underscores the importance of performing cytologic examination of skin masses, even when they seem unimportant. On necropsy, spleen, perihilar lymph nodes, liver, heart, kidneys, and trachea were also affected. Pericardial, pleural, and peritoneal effusions were also found. Gastrointestinal tract and adrenal gland involvement were reported previously15 but were not found in the present case series.

Laboratory results are nonspecific in blastomycosis in cats, as in dogs. Anemia of chronic disease is a common finding in dogs but has been reported rarely in cats with blastomycosis.15 In the present study, only 1 cat was anemic. Conceivably, chronic hypoxia may have led to increased erythropoeitin secretion and offset the anemia of chronic disease. Arterial blood gas analysis or measurement of serum concentrations of erythropoietin was not performed in any of the 8 cats of our study. High serum total protein concentration is another common finding in dogs13 and was also found in half of the cats in the present study. This could have been caused by dehydration in only 1 cat and was more likely related to high production of globulins. Hypercalcemia has been associated with granulomatous disease26 and was observed in 2 cats but was not confirmed by ionized calcium measurement.

In contrast to previous reports,4,5 final diagnosis was achieved antemortem in most cats in the present study. Cytologic examination is useful in the diagnosis of blastomycosis in dogs13 and cats4 and was accurate, easy to perform, and of high diagnostic yield. Blastomycosis in 4 cats was diagnosed via cytologic examination of skin lesions that were originally suspected to be irrelevant to the primary problem. Diagnostic aspirates were also obtained from the spleen and lungs. Diagnostic lung aspirates have been reported in dogs13 and nondomesticated cats.6 Bronchoalveolar lavage was used in 1 cat in the present study and was successful in retrieving a diagnostic sample. In a previous study,13 bronchoalveolar lavage and transtracheal aspiration were of low diagnostic yield in dogs, and they are likely to be less useful than percutaneous lung aspirates when the disease is mostly localized to the interstitium of the lung. Peripheral lymph node aspirates are useful in the diagnosis of blastomycosis in dogs.13 Peripheral lymph nodes did not seem to be involved in the disease in the cats of the present study and are not commonly reported to be infected in cats.15

Four cats in the present study died or were euthanized because of respiratory failure. Treatment was initiated in 2 of them and in the other 4 cats that survived. In previous reports, only 17%4 and 18%5 of cats with blastomycosis survived, whereas half of the cats in the present study were treated successfully, indicating that blastomycosis in cats may be more treatable than previously thought. Survival results, however, are confounded by a low rate of antemortem diagnosis in previous reports (30% to 32%4,5) and, possibly, by previous treatment with antimicrobials and glucocorticosteroids in the present report. Also, new azoles such as itraconazole and fluconazole were not available until the early 1990s. With better use of cytologic examination as a diagnostic tool for early diagnosis and with treatment with safe and effective antifungal drugs, cats with blastomycosis may now have a better prognosis.

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