Mycotic mastitis in three dogs due to Blastomyces dermatitidis

Canine blastomycosis is a common systemic fungal infection within the Ohio and Mississippi River valleys and typically presents as pneumonia, lymphadenitis, or endophthalmitis. This report describes three cases in which mammary tissue samples were submitted to the Department of Pathobiology, University of Tennessee, College of Veterinary Medicine with clinical suspicion of neoplasia or postpartum bacterial mastitis. Pyogranulomatous to granulomatous mastitis and dermatitis with intralesional yeast consistent with Blastomyces dermatitidis were diagnosed. Two of the three dogs also had lymph node and pulmonary involvement. Mycotic mastitis due to Blastomyces dermatitidis is rarely reported and blastomycosis should be considered in the differential diagnosis of dogs with mammary lesions from endemic areas.     

Osteomyelitis Associated With Disseminated Blastomycosis in Nine Dogs

Blastomycosis, a common disease entity of dogs in the southeastern United States, may be encountered elsewhere. Blastomyces dermatitidis, the cause of this disease, is a soil-borne fungal organism. B. dermatitidis is introduced into the host by inhalation of infective spores. This results in a primary lung infection. Dissemination of the organism occurs by lymphohematogenous means and may involve any body tissue. Other tissues frequently involved are the skin, male genitals, lymph nodes, eyes, and bone. Osteomyelitis was diagnosed in nine dogs with disseminated blastomycosis. Six of nine dogs had solitary bone lesions. All nine dogs had a clinical lameness. Only two dogs had clinical signs of respiratory disease. A total of 25 bone lesions were observed in these dogs, with 19 lesions located in the tubular bones of the extremities. Typically, osteolytic lesions appeared at the ends of long bones; only two lesions were observed proximal to the stifle. No extremity lesions were seen proximal to the elbow. Approximately half of the bone lesions had an associated periosteal response or soft tissue enlargement, while no sinus or fistulous tracts were observed. Blastomycosis was confirmed in all dogs by a positive reaction to the gel immunodiffusion test and/or identification of the B. dermatitidis organism. 0rganisms were retrieved and identified from a variety of tissues, including three bone biopsy specimens and one joint aspirate. In seven of nine dogs, initial diagnosis was by identification of the organism. The radiographic differential diagnoses included primary bone neoplasia, soft tissue neoplasia with secondary bone involvement, fungal osteomyelitis, and bacterial osteomyelitis. These differential diagnoses were based on the distribution, localization, and aggressiveness of the lesions observed. The 32 percent incidence of blastomycosis-associated osteomyelitis reported here is significantly higher than reported previously.     

Transtracheal aspiration in the diagnosis of pulmonary blastomycosis (17 cases: 2000-2005)

Blastomyces dermatitidis is a common etiologic agent of fungal pneumonia in dogs. Definitive diagnosis is based on cytologic demonstration of the organism in affected tissues. Fluid obtained through transtracheal aspiration has previously been reported to have a low diagnostic yield for B. dermatitidis organisms. This retrospective study identified B. dermatitidis organisms in 76% of samples when transtracheal aspiration was performed in 17 nonsedated dogs with pulmonary blastomycosis. Transtracheal aspiration is a noninvasive and simple procedure that should be considered as an early diagnostic test whenever blastomycosis is a differential diagnosis in dogs with pulmonary disease.     

Blastomycosis in a ferret

An 18-month-old female ferret with an ulcerated metacarpal pad and signs of respiratory illness was diagnosed as having blastomycosis by visualization of organisms on a tissue imprint, an agarose gel immunodiffusion test, and thoracic radiography. The ferret was treated intravenously with amphotercin B at 0.4 to 0.8 mg/kg and orally with ketoconazole at 8 mg/kg for approximately 1 month, during which time clinical and radiographic improvement was noted. A change to SC amphoterocin B therapy resulted in relapse of clinical signs despite continuation of ketoconazole therapy, and necessitated euthanasia. Necropsy revealed granulomatous lesions typical of Blastomyces dermatitidis infection in the lungs, thoracic pleura, spleen, meninges, and brain. Comparisons between this case and canine blastomycosis cases are made and alternative treatment regimes for mustelid blastomycosis are suggested.     

HYPERTROPHIC OSTEOPATHY ASSOCIATED WITH PULMONARY BLASTOMYCOSIS IN A DOG

Hypertrophic osteopathy (HO) associated with pulmonary blastomycosis was diagnosed in a 5–year-old male mixed-breed dog. One year prior to referral, increased pulmonary opacity had been identified on radiographs made during an examination for a chronic cough. Although serologic tests for blastomycosis were negative, the dog was treated with oral ketoconozole on the basis of suspicious lesions seen on radiographs and clinical signs. Ten months after completing the ketoconozole therapy, the dog was presented for a persistent cough and lameness. Intrapulmonary masses and periosteat proliferation were observed radiographically. A biopsy of the pulmonary masses was done, and Blastomyces dermatitidis was identified. Amphotericin B and ketoconozole administration resulted in clinical improvement and partial resolution of the HO lesions five months after initiation of therapy.     

Ocular changes in a cat with disseminated blastomycosis

A domestic shorthair cat examined because of dyspnea was found to have ophthalmoscopic and radiographic changes suggestive of systemic mycosis. The cat died despite antifungal therapy. Histologic examination revealed Blastomyces dermatitidis in the eyes, brain, lungs, stomach, liver, kidneys, spleen, pancreas, and adrenal glands. The pathologic changes were similar, but more widespread than those typically seen with canine blastomycosis.     

Blastomycosis in nondomestic felids.

Blastomycosis was diagnosed in six nondomestic felids from eastern Tennessee, including two Asian lions (Panthera leo persicus), one African lion (Panthera leo), one Siberian tiger (Panthera tigris), one cheetah (Acinonyx jubatus), and one snow leopard (Panthera uncia). Clinical signs included lethargy, anorexia, weight loss, dyspnea, sneezing. ataxia, and paresis. Variable nonspecific changes included leukocytosis, monocytosis, moderate left shift of neutrophils, moderate hypercalcemia, hyperproteinemia, and hyperglobulinemia. Thoracic radiographs revealed interstitial and alveolar changes, consolidation or collapse of a lung lobe, bullae formation, and a pulmonary mass. Agar gel immunodiffusion (AGID) serology for Blastomyces dermatitidis was performed in five felids and was positive in three. The tiger had cerebral blastomycosis and was positive for AGID serologic tests of both cerebrospinal fluid and serum. One percutaneous lung aspirate in the snow leopard and one bronchial aspirate in an Asian lion demonstrated B. dermatitidis organisms. whereas tracheal wash samples and a nasal discharge were nondiagnostic in others. Treatment with itraconazole was attempted in four cats. The tiger improved before euthanasia, whereas the others did not survive beyond initial treatments. In four felids, B. dermatitidis was found in the lungs and tracheobronchial lymph nodes associated with a florid pyogranulomatous reaction; the tiger had a pyogranulomatous encephalomyelitis, and the cheetah had a single pulmonary granuloma. Thoracic radiography, cytologic examination of lung lesion aspirates, and B. dermatitidis AGID serology should be performed on clinically ill zoo felids in endemic areas to rule out blastomycosis.     

Cultural and histopathologic confirmation of canine blastomycosis diagnosed by an agar-gel immunodiffusion test

Sixteen sera from 17 dogs with blastomycosis produced a precipitin band identical with the diagnostically significant precipitin A band formed by a Blastomyces dermatitidis reference antiserum and a soluble B dermatitidis yeast-form antigen in the agar-gel immunodiffusion test (94% sensitivity). The other serum from a dog with histopathologic demonstration of B dermatitidis in pulmonic tissues produced an unrelated precipitin band. Sixteen of the 17 diagnoses made by the detection of precipitin A were confirmed by isolation and culture of B dermatitidis or by histopathologic demonstration of the pathogen. Three cases were confirmed by cultural isolation only, 10 by histopathologic demonstration only, and 3 by both. In three other dogs given amphotericin B, there were demonstrable changes in serum precipitin A reactions.     

Antigen and antibody testing for the diagnosis of blastomycosis in dogs

BACKGROUND: Early diagnosis and treatment are associated with an improved prognosis in blastomycosis. The diagnosis of blastomycosis may be missed by cytology, histopathology, culture, or serology. An enzyme immunoassay (EIA) for detection of Blastomyces dermatitidis galactomannan antigen in body fluids has been used for rapid diagnosis of blastomycosis in humans. HYPOTHESIS: Measurement of Blastomyces antigen in urine or serum by the MVista Blastomyces antigen EIA is more sensitive than measurement of anti-Blastomyces antibodies for diagnosis of blastomycosis in dogs. METHODS: Serum and urine samples from 46 dogs with confirmed blastomycosis were tested for Blastomyces antigen and serum was tested for anti-Blastomyces antibodies. RESULTS: The sensitivity for the detection of antigen in urine was 93.5% and it was 87.0% in serum. The sensitivity of antibody detection by agar gel immunodiffusion (AGID) was 17.4% and it was 76.1% by EIA. Antigen and antibody decreased during itraconazole treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: Antigen detection is a more sensitive test for diagnosis of blastomycosis than antibody testing by AGID, the only commercially available method. Antigen concentrations decreased with treatment.     

Disseminated blastomycosis in two California sea lions (Zalophus californianus).

Two captive California sea lions (Zalophus californianus) from different facilities were diagnosed with disseminated blastomycosis. The first, a 12-yr-old male, died after a 3-wk history of progressive anorexia and lethargy. Gross examination revealed acute jejunitis with focal perforation and associated peritonitis, along with severe purulent bronchopneumonia. The second, a 15-yr-old female, was euthanized after a 2-wk history of severe cutaneous ulceration and declining clinical condition. Gross examination revealed severe pyogranulomatous bronchopneumonia and ulcerative dermatitis. Histopathologic examination in both individuals revealed severe multifocal subacute to chronic pyogranulomatous pneumonia associated with massive numbers of fungal organisms morphologically compatible with Blastomyces sp. Fungal organisms were 8-20-microm-diameter broad-based budding yeasts with thick, refractile, double-contoured walls. The male sea lion had multifocal transmural Blastomyces-induced enteritis with subsequent rupture and peritonitis. The organism was also present in the liver, with minimal associated inflammation. The female had severe multifocal pyogranulomatous ulcerative dermatitis associated with large numbers of intralesional fungal organisms. Dissemination to the spleen had occurred in both animals. A serologic immunodiffusion test for Blastomyces dermatitidis was positive in the male. The presumptive primary pathogen in both cases was Blastomyces dermatitidis.     

Canine antibody response to Blastomyces dermatitidis WI-1 antigen

OBJECTIVE: To assess whether dogs with blastomycosis produce antibodies against the WI-1 and A-antigens of Blastomyces dermatitidis and whether the antibodies are useful in serodiagnosis. SAMPLE POPULATION: 359 serum samples obtained from 245 dogs. PROCEDURE: 233 samples from 122 dogs with blastomycosis, and 1 sample each from 24 dogs with suspected blastomycosis, 51 control dogs without infection, and 48 healthy dogs from an enzootic region were obtained. Antibodies against WI-1 antigen were detected by radioimmunoassay (RIA). Serum samples were tested in parallel for antibodies against the A-antigen of B dermatitidis by commercial agar-gel immunodiffusion (AGID) in a reference laboratory. RESULTS: Antibodies were detected in 92% of infected dogs by RIA and in 41 % by AGID. For 29 serum samples that were obtained 11 to 1,545 days after diagnosis, antibodies were detected in 92% of samples by RIA and 7% by AGID. For 93 serial serum samples from 29 dogs with blastomycosis, the mean anti-WI-1 titer was 1:18,761 at the time of diagnosis, and decreased to a mean of 1:1,338 by 210 days after treatment was initiated. Of 24 dogs with suspected infection, antibodies were detected in 67% by RIA and 33% by AGID. Control dogs without blastomycosis had no detectable antibodies in either assay. Thus, sensitivity was 92% for RIA and 41 % for AGID, and specificity was 100% for both tests. CONCLUSIONS AND CLINICAL RELEVANCE: Anti-WI-1 antibodies are readily detected by RIA in dogs with blastomycosis. Titers become high, decline during treatment, and persist for months. Anti-A antibodies are sometimes detected with AGID, but these decrease quickly.     

Counterimmunoelectrophoresis (immunoelectroosmosis) and serum electrophoretic pattern in serologic diagnosis of canine blastomycosis

Counterimmunoelectrophoresis (CIEP) with blastomyces and histoplasma antigens was used in a serologic study of 181 dogs clinically suspected of having blastomycosis and of 8 dogs with confirmed blastomycosis or histoplasmosis. Thirteen of the 181 dogs, positive by CIEP, were euthanatized, and the diagnosis was confirmed by cultivation and/or microscopic detection of Blastomyces dermatitidis. Additional CIEP-positive dogs were confirmed by staining of aspirates collected in vivo. Radiographic support for the diagnosis was reported in 4 other dogs in which histoplasmosis was excluded by a negative CIEP with histoplasma antigen. The precipitating antibody may disappear during the course of the disease, as it did in 1 dog treated with amphotericin B, but not cured. This dog reverted from CIEP-positive to CIEP-negative within 17 months of treatment (with a weak reaction after 10 months of treatment). The CIEP-detectable antibody was present only in 1 dog without a confirmation by histopathologic findings or cultivation among 24 well-documented cases and 181 total tested sera. The CIEP was more sensitive and specific than was the gel-diffusion precipitin test, eliminated the problems of anticomplementarity that often affected the results of complement-fixation tests with canine sera, and served well in detecting dogs with blastomycosis. Electrophoretic pattern of sera from CIEP-positive dogs with blastomycosis showed a decrease in albumin and an increase in alpha 2- and often in beta- and gamma-globulins, with a substantial decrease of the albumin/globulin ratio.     

Comparison of histologic lesions of endophthalmitis induced by Blastomyces dermatitidis in untreated and treated dogs: 36 cases (1986-2001)

OBJECTIVE: To compare prevalence of organisms and histologic changes in eyes from dogs with blastomycosis that were either untreated or undergoing treatment with itraconazole. DESIGN: Retrospective study. ANIMALS: 36 dogs with endophthalmitis associated with blastomycosis. PROCEDURE: Signalment, results of ophthalmic examination, and duration of treatment with itraconazole were extracted from medical records. Histologic sections from eyes were examined for prevalence and viability (ie, budding) of fungal organisms. A scoring system was devised to assess the degree of inflammation. RESULTS: Clinically, all eyes were blind and had signs of severe endophthalmitis. Histologically, the type and degree of inflammation and prevalence of Blastomyces dermatitidis were not significantly different between dogs treated with itraconazole and untreated dogs or among groups of dogs treated for different time periods (4 to 14, 15 to 28, or 29 to 72 days). Replication of the organisms in vascular tissues as well as avascular spaces in the eyes was similar in treated and untreated dogs. Lens rupture was seen in 12 of 29 (41%) eyes. CONCLUSIONS AND CLINICAL RELEVANCE: Persistence of inflammation in eyes of dogs with naturally occurring blastomycosis is likely attributable to the continued presence of B. dermatitidis, regardless of the duration of treatment with itraconazole. Lens capsule rupture, a common and previously unreported histologic finding, may contribute to cataract formation and continued inflammation.     

Epidemiology, diagnosis, and treatment of blastomycosis in dogs and cats

Blastomycosis is one of the most common systemic fungal diseases in dogs in North America, but it is rarely diagnosed in cats. The typical route of infection is inhalation of aerosolized conidia of Blastomyces dermatitidis. From the respiratory tract, the developing yeast form may disseminate throughout the body and affect multiple organ systems, most commonly the lymphatic, skeletal and central nervous systems, eyes and skin. Disseminated disease often is associated with nonspecific signs of illness including lethargy, inappetence and fever, as well as signs referable to specific organ systems like chronic cough and dyspnea, peripheral lymphadenopathy, endophthalmitis, and central nervous signs. Diagnosis is typically made by detection of Blastomyces dermatitidis yeast in affected tissues by fine-needle aspiration cytology or histopathology. The treatment of choice is itraconazole. Prognosis is fair in dogs without central nervous disease and guarded in cats.     

Pleural effusion secondary to thoracic metastatic mammary adenocarcinoma in a mare

A 17-year-old Quarter Horse mare was examined nearly 3 years after excision and cryotherapy of a papillary mammary gland adenocarcinoma. The mare had been used for pleasure riding since surgery, but had recently developed progressive dyspnea. The mare had clinical evidence of pleural effusion, but died before further clinical examination and treatment were instituted. Necropsy revealed deep mammary masses with similar nodules in the deep inguinal, renal, and mediastinal lymph nodes and in the lungs, pericardium, visceral and parietal pleurae, and left ovary. The masses were identified as papillary mammary gland adenocarcinoma. Large volumes of free pleural and peritoneal fluid were detected. The pleural fluid contained similar neoplastic cells that could have been readily detected by exfoliative cytologic examination had the mare survived.     

Ultrasound-Guided Fine-Needle Aspiration of Focal Parenchymal Lesions of the Lung in Dogs and Cats

Ultrasound-guided fine-needle aspiration (FNA) of the lung was performed on 16 dogs and 3 cats with consolidated pulmonary lesions or masses identified on thoracic radiographs. The cytologic results from the FNA were confirmed by histopathology, response to treatment, or microscopic identification of Blastomyces organisms. Neoplasia was identified correctly by FNA cytology in 10 of 11 animals, and no false positive results occurred, yielding a positive predictive value of 100%. Of 8 animals with infectious disease, 5 of 6 had blastomycosis and 1 had a bacterial infection, based on cytologic evaluation. Eight animals required sedation for the procedure, and none had clinical complications. We conclude that ultrasound-guided FNA of pulmonary mass lesions is an inexpensive, safe, and accurate method for diagnosing blastomycosis or neoplasia, especially carcinomas, in dogs and cats.     

Cerebral Blastomyces dermatitidis infection in a cat

CASE DESCRIPTION: An 8-year-old domestic shorthair cat was evaluated because of signs of depression, circling, and visual deficits. CLINICAL FINDINGS: The cat had no cutaneous lesions, and results of an ophthalmologic examination and thoracic radiography were within reference limits. Computed tomography of the brain revealed a mass lesion involving the right parietal, temporal, and occipital lobes; the mass was in broad-based contact with the skull and smoothly marginated and had strong homogenous enhancement after contrast agent administration. During craniectomy, samples of the mass were collected for cytologic and histopathologic evaluations and microbial culture. A diagnosis of Blastomyces dermatitidis-associated meningoencephalitis with secondary pyogranulomatous inflammation was made. TREATMENT AND OUTCOME: Amphotericin B (0.25 mg/kg [0.11 mg/lb], IV) was administered on alternate days (cumulative dose, 1.75 mg/kg [0.8 mg/lb]). To minimize the risk of nephrotoxicosis, assessments of serum biochemical variables (urea nitrogen and creatinine concentrations) and urinalyses were performed at intervals. The third dose of amphotericin B was postponed 48 hours because the cat became azotemic. The cat subsequently received fluconazole (10 mg/kg [4.5 mg/lb], PO, q 12 h) for 5.5 months. Six months after discontinuation of that treatment, the cat appeared healthy and had no signs of relapse. CLINICAL RELEVANCE: Brain infection with B dermatitidis is typically associated with widespread disseminated disease. The cat of this report had no evidence of systemic disease. Blastomycosis of the CNS should be considered as a differential diagnosis for brain lesions in cats from areas in which B dermatitidis is endemic.     

Diagnostic peritoneal lavage for identification of blastomycosis in a dog with peritoneal involvement

A 6-year-old castrated male Dalmatian was evaluated because of hematemesis. The dog had lived its entire life in South Dakota and Wyoming and had never traveled outside of these states. Results of laboratory testing were compatible with iatrogenic acute renal failure and gastrointestinal tract ulceration secondary to previous nonsteroidal anti-inflammatory drug and corticosteroid administration. Differential diagnoses for clinical signs and laboratory abnormalities that existed prior to these treatments included multisystemic infectious or inflammatory disease and neoplasia. Four-quadrant abdominocentesis did not yield any fluid, but because intra-abdominal disease was still suspected, diagnostic peritoneal lavage was performed. Fluid that was obtained was markedly cellular, and there were numerous extracellular structures with a round to oval shape; a 1-microm-thick, clear-staining capsule; a basophilic interior; and broad-based budding. Organisms were consistent with Blastomyces spp, and fungal culture yielded Blastomyces dermatitidis. Treatment with liposomal amphotericin B and itraconazole was recommended but could not be initiated because of the client's financial constraints. At necropsy, disseminated blastomycosis involving the stomach, small intestines, urinary bladder, omentum, mesentery of the small intestine, and abdominal wall musculature was seen. To our knowledge, peritoneal involvement has not been reported in dogs with blastomycosis, and gastrointestinal tract involvement has only rarely been reported. Findings in this dog suggest that diagnostic peritoneal lavage may be a useful technique in determining the cause of infectious peritonitis when the amount of abdominal fluid is below the limit of detection for abdominocentesis.     

Arterial thromboembolic disease in a dog with blastomycosis localized in a hilar lymph node

An 8-year-old mixed-breed dog was evaluated for caudal paresis. Transient lameness of the left hind and left forelimbs had developed during the preceding week. Clinical findings included conscious proprioceptive deficits, hyporeflexive tendon reflexes and decreased pain perception, coolness in the hind limbs and left forelimb, and absence of femoral pulses. A fluid-dense mass was radiographically identified adjacent to the left atrium. Echocardiography revealed a mass in the left atrium and spontaneous contrast in the left ventricular lumen and aortic root. The dog was euthanatized because of its deteriorating condition. A large mass was adhered to the dorsal left atrial wall and had eroded into the atrial lumen. A sterile blood clot was attached to this site, and sterile thrombi were in the terminal portion of the aorta. Histologically, the mass was found to be hilar lymph node with chronic pyogranulomatous inflammation containing organisms characteristic of Blastomyces dermatitidis.