Blastomyces dermatitidis Prostatic and Testicular Infection in Eight Dogs (1992–2005)
This was a retrospective case study of eight dogs diagnosed with prostatic or testicular B. dermatitidis infection. Signalment, clinical presentation, diagnostic procedures, and treatment options were evaluated. Review of medical records of dogs diagnosed with blastomycosis at the University of Illinois Veterinary Teaching Hospital from 1992 to 2005 yielded four dogs with prostatic blastomycosis (PB) and four dogs with testicular blastomycosis (TB). Three of the four dogs with PB and all four dogs with TB had evidence of urogenital disease. Three dogs with PB had an elevated body temperature and all had systemic disease. All dogs with TB had a normal body temperature, and three had systemic disease and one had clinical signs limited to testicular disease. Cytology or histopathology was used to diagnose PB or TB. Treatment included itraconazole or fluconazole with or without nonsteroidal anti-inflammatory drugs. PB and TB are infrequently recognized and may be under diagnosed due to failure to specifically evaluate these tissues. PB or TB should be considered in the evaluation and staging of male dogs with blastomycosis. Male dogs with urogenital signs should be evaluated via prostatic or testicular cytology or histopathology since proper identification and management of PB or TB may improve overall treatment success.
Introduction
Blastomyces dermatitidis is a saprophytic, dimorphic fungal organism existing in the environment as a mycelial form in soil and as a yeast form in infected body tissues.1 Entry into the body is via inhalation of aerosolized spores or transcutaneous inoculation with subsequent uptake by macrophages, where B. dermatitidis transforms from the mycelial phase to the yeast phase.2,3 The most commonly reported sites of involvement include lungs, lymph nodes, integument, eye, and bone. Urogenital, central nervous system, and cardiac involvement have been reported less frequently.3–5
Published reports specifically focused on canine urogenital blastomycosis are few and include one case report of a dog that was euthanized without treatment and a report of prostatic blastomycosis (PB) diagnosed postmortem.6,7 In a retrospective study of blastomycosis in 115 dogs, the testes were affected in 10 of 58 (17%) intact male dogs, and the prostate was affected in 2 of 58 (3%) intact male dogs.3 Specific management of the testicular and prostatic cases was not discussed. In a study of 177 cases of prostatic disease in dogs, prostatitis attributable to blastomycosis was diagnosed in one case (0.6%), and the details of this case were not discussed.8 Prostatic or testicular lesions were reported in one of six (16%) dogs with experimentally induced disseminated blastomycosis.9 In human blastomycosis, the genitourinary system is involved in 20–30% of systemic infections, and, in one report of human urogenital blastomycosis, infection was limited to the prostate in 50% of 81 cases.1,10–13
Canine urogenital blastomycosis may occur more frequently than is recognized because specific diagnostics to evaluate for urogenital infection are not performed. Recognition of urogenital involvement is important to allow for optimal therapeutic management and monitoring. The present study describes eight cases of confirmed B. dermatitidis infections involving the prostate or testes in dogs. The purpose of this article is to evaluate the signalment, clinical signs, diagnostic procedures, and factors impacting selection of antifungal drugs and adjunctive therapies for PB or testicular blastomycosis (TB).
Materials and Methods
The Veterinary Medical Database (VMDB) was searched to identify medical records of dogs diagnosed with blastomycosis at the University of Illinois from 1992 to 2005.† Only patients with PB or TB confirmed by cytologic or histopathologic detection of B. dermatitidis yeast organisms were included in this study.
Procedures
Records for dogs diagnosed with TB and/or PB were evaluated for signalment, clinical signs, physical examination findings (including ophthalmic evaluation), and clinical pathology results (complete blood count, chemistry profile, and urinalysis). Imaging diagnostics (radiography and ultrasonography) and diagnostic procedures (fine needle aspiration with cytology or biopsy with histopathology), days of hospitalization, treatment regimen, and outcome were recorded.
Results
Affected Dogs
Of 155 cases, 86 were male, of whom 37 were intact. Of the 86, the prostate was evaluated in only 5, and of those, 4 were confirmed to have PB. Of the 37 intact dogs, testes were evaluated in only 4 dogs, and of those, 4 were confirmed to have blastomycosis. TB was identified in three German shepherd dogs (GSDs) and one Labrador retriever. The mean age at diagnosis was 3.1 yr (1.5–4 yr). PB was identified in one standard poodle, one Bernese mountain dog, one beagle, and one Belgian sheepdog. Two of the four dogs with PB were sexually intact at the time of presentation. The mean age at diagnosis was 5.25 yr (2–8 yr). Length of illness before diagnosis ranged from 2 wk to 8 wk.
Clinical Presentation
Testicular Blastomycosis Dogs
Three of the four dogs with TB (Table 1) had systemic signs of disease, including exercise intolerance (n=2), increased respiratory effort (n=2), weight loss (n=3), hyporexia (n=2), peripheral lymphadenopathy (n=2), and nonproductive cough (n=1). One dog had scrotal swelling, but with no evidence of systemic infection. Three dogs had scrotal swelling, and the other dog had a palapable 3 mm nodule on the caudal pole of the left testicle. Of the three dogs with scrotal swelling, one had scrotal swelling reported in the history and had been neutered 1 wk before presentation, at which time histopathology had been performed on the testes. Body temperature of the four dogs with TB was normal, ranging from 101.8°F to 102.4°F (37.8–39.1°C). All TB dogs had normal findings on ophthalmologic examination.
GSD, German shepherd dog.
1, hyporexia; 2, increased respiratory effort; 3, exercise intolerance; 4, weight loss; 5, peripheral lymphadenopathy; 6, weakness; 7, hematuria; 8, emesis; 9, dysuria; 10, skin lesions; 11, scrotal swelling; 12, testicular nodule; 13, nonproductive cough.
Prostatic Blastomycosis Dogs
All four dogs with PB (Table 2) had systemic signs of infection, including exercise intolerance (n=2), increased respiratory effort (n=1), weakness (n=1), hyporexia (n=3), weight loss (n=2), nonproductive cough (n=1), emesis (n=1), and lymphadenopathy (n=3). Three of the four dogs with PB infection had clinical signs of urogenital disease, manifested as dysuria due to urethral obstruction in two dogs and hematuria in one dog. Both dogs with dysuria had been neutered the week before presentation in an effort to relieve their dysuria; one of these dogs had swollen testicles with scrotal wounds at the time of neutering, but histopathology of the testicles had not been performed. Body temperature of three of four dogs with PB was elevated, ranging from 103.0°F to 104.0°F (39.4–40.0°C). An ophthalmologic evaluation revealed fundic granulomas and retinal detachment in both eyes in the Bernese mountain dog with PB. This dog did not have clinical signs of ocular disease and was reportedly visual. The three other dogs with PB were normal on ophthalmologic examination.
1, hyporexia; 2, increased respiratory effort; 3, exercise intolerance; 4, weight loss; 5, peripheral lymphadenopathy; 6, weakness; 7, hematuria; 8, emesis; 9, dysuria; 10, skin lesions; 11, scrotal swelling; 12, testicular nodule; 13, nonproductive cough.
Diagnostic Evaluation: Clinical Pathology
A complete blood count and chemistry profile were performed on all eight dogs. The chemistry profile results for all dogs were unremarkable, except for two dogs with elevated alkaline phosphatase of 650 g/dL (Table 1, dog 4) and 291 g/dL (Table 2, dog 1) (reference range, 12–110 g/dL). The complete blood count results were abnormal for one TB dog and two PB dogs. The TB dog (Table 1, dog 1) had a leukocytosis of 25.7×103 cells/μL (reference range, 6.0–17.0×103 cells/μL), with a mature neutrophilia. One of the PB dogs (Table 2, dog 1) had a leukocytosis of 34.6×103 cells/μL with 29.4×103 cells/μL mature neutrophils, and the other (dog 3) had a leukocytosis of 22.0×103 cells/μL with 15.84×103 cells/μL of mature neutrophils characterized with a left shift of 3.52×103 cells/μL band neutrophils. A urinalysis was performed on six of the eight dogs and revealed normal findings. Of the four dogs with PB, the urine specific gravity ranged from 1.020 to 1.044, with a urine pH ranging from 6.0 to 8.0. One of the two dysuric PB dogs (Table 2, dog 4) had a urine culture performed that yielded no growth.
Diagnostic Evaluation: Imaging
All eight dogs showed thoracic radiographic abnormalities consistent with disseminated blastomycosis. All PB dogs had diffuse bronchointerstitial and focal nodular lung patterns, but none of these dogs had clinical signs of respiratory disease. Two TB dogs (Table 2, dogs 1 and 2) had a diffuse interstitial lung pattern but no clinical signs of respiratory disease. The other 2 TB dogs had clinical signs of respiratory disease (cough and increased respiratory effort), as well as radiographic abnormalities: one dog (dog 4) had pleural effusion and a diffuse interstitial pattern, and the other (dog 3) had a mass effect in the left cranial lung lobe.
All four PB cases had an abdominal ultrasound performed with prostatomegaly observed in the standard poodle and Belgian sheepdog; diffuse heterogenicity with prostatomegaly was observed in the beagle and Bernese mountain dog. One of the TB cases (4 yr old intact GSD) had an abdominal ultrasound and an enlarged, diffusely coarse or heterogenous prostate was observed.
Diagnostic Evaluation: Cytologic Evaluation and Other Procedures
The TB dog (Table 1, dog 3) with the left cranial lung lobe mass effect had a palpable firm, 3.0 mm nodule on the caudal pole of the left testicle. Fine needle aspiration and cytology of the testicular mass revealed pyogranulomatous inflammation with no infectious organisms observed. This dog also had a thoracic computed tomographic scan that showed a heart base mass; computed tomographic directed fine needle aspiration and cytology of the mass was nondiagnostic (yielded blood only). A thoracotomy was performed, and the mass was resected at the same time as castration and scrotal ablation were performed for the testicular mass. Histopathology of the lung mass revealed pyogranulomatous inflammation; no infectious organisms were seen, but Blastomyces was identified on histopathologic evaluation of the testicular mass. Blastomycosis was presumed to be the cause of the pyogranulomatous intrathoracic disease in this dog based on the positive findings in the testicle.
Two of the TB (Table 1) and two of the PB (Table 2) dogs had lymphadenopathy with blastomycosis diagnosed on lymph node aspiration and cytology. In dogs with TB (Table 1), a definitive diagnosis was obtained via testicular aspiration cytology or testicular histopathology and demonstration of Blastomyces organisms. None of the TB dogs had further diagnostics performed to evaluate for PB. All four PB dogs were further evaluated with prostatic fine needle aspiration and cytology; B. dermatitidis organisms were identified in three of the four PB dogs (Table 2). The Bernese mountain dog had prostatic and testicular aspiration that failed to identify an etiology (the prostatic aspirate sample was hemodiluted/nondiagnostic and testicular cytology was normal). A prostatic wash sample from this dog was evaluated by cytology and fungal culture. B. dermatitidis organisms were present in the cytology sample, but fungal culture yielded no growth.
Treatment and Outcome
Testicular Blastomycosis Dogs
The TB dog with pleural effusion died shortly after therapeutic chest tube placement. The TB dog that had the thoracotomy performed was treated with 6.5 mg/kg of itraconazole (Sporanoxa) q 12 hr; this dog had no evidence of disease 4 mo after diagnosis, and the itraconazole was continued for an additional 2 mo. The other two TB dogs were alive at the time of discharge from the hospital. One dog (Table 1, dog 2) was discharged with 6.0 mg/kg of itraconazole q 24 hr and buffered aspirin in an effort to decrease inflammation. The other dog (Table 1, dog 1) was discharged with the recommendation to begin itraconazole treatment. Both of these dogs were lost to follow up.
Prostatic Blastomycosis Dogs
One of the two PB dogs (Table 2, dog 1) with urethral obstruction was euthanized after being diagnosed with PB. The other dog (Table 2, dog 4) with urethral obstruction had a closed urinary catheter system placed for 48 hr, after which the catheter was removed. Dysuria recurred and the urinary catheter was replaced for another 48 hr. This dog was initially treated with 5.0 mg/kg of itraconazole q 24 hr but treatment was changed to 5.0 mg/kg of fluconazole (Diflucanb) q 12 hr because of concerns regarding possible poor drug penetration of itraconazole into the prostate. Carprofen (Rimadylc) 2.5 mg/kg q 12 hr for 2 wk was prescribed for this dog in an effort to decrease inflammation. This dog was urinating normally after 8 days of hospitalization and was discharged. No further problems occurred during the follow-up period of 4 mo. Of the other two PB dogs, one was lost to follow up (Table 2, dog 3), and the other dog (Table 2, dog 2) was treated with 6 mg/kg of itraconazole q 24 hr and had a ultrasonographically normal prostate at the 2 mo recheck but was subsequently lost to follow up.
Discussion
Male dogs with blastomycosis may have involvement of the prostate gland or testicles and may or may not have clinical signs attributable to urogenital disease or systemic infection. In this study, one dog with PB had no clinical signs of urogenital disease, which might have prompted further evaluation of the urogenital system. Additionally, one dog with TB did not have clinical signs of systemic blastomycosis. Dogs with PB may present with urinary signs, such as hematuria, pollakiuria, and dysuria. Symptoms of TB may include swollen testes, scrotal wounds, or a testicular nodule. The consideration of blastomycosis as a differential for primary urogenitial disease is important because the treatment needs to be specific for fungal infection. Also, urogenital blastomycosis needs to be considered in dogs diagnosed with systemic disease. Histopathology should be performed on all testes with pathology after castration. Also, male dogs diagnosed with systemic blastomycosis should have a thorough urogenital evaluation, including prostatic and testicular evaluation via ultrasound and needle aspiration with cytology because urogenital blastomycosis can occur without clinical symptoms.
Urogenital infection, and specifically prostatic or testicular infection, may be established by multiple routes, which include ascending urinary tract infection, dissemination of systemic infection, penetration of scrotal skin, and extension of infection from adjacent tissues.14 Seven of eight dogs in this study had evidence of systemic involvement (pulmonary changes or lymphadenopathy), suggesting the more typical route of dissemination via inhalation of aerosolized spores and hematogenous spread.
The prevalence of concurrent PB and TB infections is not known. Only one dog in the present study had concurrent evaluation of the prostate and testicles via needle aspiration with cytology. Two of the dogs with PB had been neutered before presentation due to abnormalities of the testes or scrotum, but histopathologic evaluation had not been performed, so testicular involvement could not be assessed. Eleven of 51 cases of human systemic blastomycosis had genitourinary tract disease, including the prostate (n=8) or epididymis and testes (n=6). Therefore, prostate and epididymis/testicular involvement occurred simultaneously in a few of these cases.10 In another human case report, blastomycosis was diagnosed in the prostate and epididymis without systemic involvement and treated with ketoconazole.11 The occurrence of simultaneous PB and TB in dogs should be considered, and further investigation of either organ should be performed to determine the extent and staging of the disease.
In the present study, three of four dogs with TB were GSDs. Epidemiologic studies have shown a number of dog breeds, including the Doberman pinscher, Labrador retriever, GSD, Weimaraner, pointers, cocker spaniel, bluetick coonhound, and Treeing Walker coonhound, to be overrepresented among blastomycosis cases.3,15 In GSDs, breed-associated immunoglobulin-A (Ig-A) deficiency may predispose dogs to various infections of the skin, respiratory, gastrointestinal, and urogenital systems.16 Altered immunocompetence has been speculated to play a role in susceptibility of dogs with blastomycosis.3 Also, in a series of 12 cases of disseminated aspergillosis in 11 GSDs and 1 Dalmatian, serum IgA levels were decreased in 30% of cases.17 An IgA deficiency should be considered a predisposition to developing systemic blastomycosis infection and possibly predisposition to urogenital involvement.
Prostatic ultrasound with fine needle aspiration cytology of the prostate proved to be a valuable test in elucidating a diagnosis of PB in all four dogs in the study population. In a recent human case report, PB was diagnosed via prostate needle biopsy.12 Because only 35 of 155 blastomycosis patients reviewed for the present study were evaluated by abdominal ultrasound, the overall diagnostic usefulness of this procedure in evaluating blastomycosis patients was uncertain. It is possible that a more consistent use of abdominal ultrasonography to evaluate patients with blastomycosis for the extent of their disease and following through with appropriate diagnostics (collection of cytology or biopsy samples) would identify urogenital involvement in a larger number of dogs.
Despite equivalent treatment, male dogs with blastomycosis have been reported to have a lower survival rate than female dogs.18 It should be considered that failure to identify urogenital involvement and to adapt treatment protocols to address testicular and prostatic infection contribute to a less favorable outcome for male dogs as a result of persistent disease in the prostate or testicle serving as a nidus of infection. Because host defenses are limited in the prostate, infection can persist and potentially serve as a nidus for further spread of infection to other tissues.19 The central nervous system, the eye, and the prostate gland have nonfenestrated capillary beds that impose challenges to drug penetration. Also, in the prostate gland, pH partition is a factor for achieving appropriate drug concentration. Weak basic drugs accumulate in higher concentration in the prostate compared with plasma due to the acidic prostatic secretions.20 In a human study evaluating fluconazole penetration into prostatic fluid, it was speculated that the low molecular weight and minimal protein binding were the reasons for comparable prostatic fluid and serum fluconazole concentration despite fluconazole's low lipid solubility.21 Further investigation is needed to determine relative efficacy of fluconazole or itraconazole for treatment of dogs with PB.
Castration with scrotal ablation was performed in all TB cases in this study and is likely to be beneficial in removing a source of discomfort and nidus of infection in tissue that otherwise may be difficult to clear because of immune privilege. Another treatment consideration is the benefit neutering may have on improving resolution of blastomycosis prostatic infection based on the findings in a study of the effects of castration on chronic bacterial prostatitis in dogs. In this study, dogs with experimentally induced Escherichia coli prostatitis that were neutered and treated with antibiotics had a mean infection duration of 4.2 wk compared with the intact, control group with a 9.5 wk duration of infection.22 Neutering dogs with blastomycosis in addition to antifungal drug administration may have a twofold effect on resolution by removing a possible nidus of infection in the testes and the possibility for improved resolution of prostatic infection. Also, whether adequate drug levels in testicular tissues are achieved by administration of commonly used antifungal agents has not been reported for dogs.
In conclusion, prostatic or testicular infection with B. dermatitidis appears to be infrequently recognized and occurs in association with disseminated disease and involvement of other organs, especially the lungs. Male dogs may have a lower survival rate compared with female dogs when treated for blastomycosis due to PB or TB infection. PB or TB infection should be considered in the evaluation and staging of male dogs with blastomycosis. Abdominal ultrasound and prostatic needle aspiration should be considered in the staging of dogs diagnosed with blastomycosis. Further investigation, including prostatic and/or testicular cytology or histopathology of testicular lesions, is necessary in evaluation of dogs with urogenital symptoms. Treatment and monitoring may be tailored for prostatic or testicular involvement. Proper identification and management of these infections may improve overall treatment success in male dogs with blastomycosis.
Contributor Notes
A. Totten's present affiliation is the Northeast Indiana Veterinary Emergency and Specialty Hospital, Fort Wayne, IN.
