A case of disseminated blastomycosis with pulmonary, genitourinary, and osteoarticular involvement in southern Saskatchewan

A case of disseminated blastomycosis with pulmonary, genitourinary, and osteoarticular involvement in Southern Saskatchewan | Jammi: Official Journal of the Association of Medical Microbiology and Infectious Disease CanadaA case of disseminated blastomycosis with pulmonary, genitourinary, and osteoarticular involvement in southern Saskatchewan
Karen Bennie Ho MD1, Maxwell Ng BHSc2, Kelsey Tallon MB, BCh, BAO, FRCPC1,3
Although southern Saskatchewan is not known to be a region endemic to blastomycosis, we present a case of disseminated blas- tomycosis in a 39-year-old man with pulmonary, genitourinary, and osteoarticular involvement. The patient presented with persistent fevers despite recent antibiotic therapy, arthritis in his left foot, and urinary obstruction. A computed tomography (CT) scan of the chest revealed a diffuse miliary pattern. A transbronchial biopsy only showed granulomatous changes, and washings were negative for fungal culture. Magnetic resonance imaging (MRI) of the left foot revealed signs of septic arthritis. Pathology from the joint aspiration and debridement revealed budding yeast in keeping with blastomycosis. Urine culture also grew blastomycosis, confirming urinary involvement. He was initiated on itraconazole, with complete resolution of his symptoms within 2 weeks. This case illustrates the chal- lenges in diagnosing disseminated blastomycosis, and further establishes the endemicity of blastomycosis in southern Saskatchewan.
KEY WORDS: Blastomyces, blastomycosis, fungal infection, Saskatchewan
Même si le sud de la Saskatchewan n’est pas réputé être une région où la blastomycose est endémique, les auteurs présentent un cas de blastomycose disséminée chez un homme de 39 ans, comportant une atteinte pulmonaire, génito-urinaire et ostéoarticulaire. Cet homme a consulté à cause d’une fièvre persistante malgré une récente antibiothérapie, de l’arthrite dans le pied gauche et une occlusion urinaire. La tomodensitométrie pulmonaire a révélé une atteinte miliaire diffuse. La biopsie transbronchique a seulement démontré la présence de changements granulomateux, et les lavages étaient négatifs à la culture fongique. L’imagerie par résonance magnétique (IRM) du pied gauche a indiqué la présence de signes d’arthrite septique. La pathologie de l’aspiration articulaire et du débridement a révélé des levures à bourgeonnement évocatrices d’une blastomycose. La culture d’urine a également fait proliférer une blastomycose, ce qui a confirmé l’atteinte urinaire. Le patient a pris de l’itraconazole, et ses symptômes ont complètement dis- paru au bout de deux semaines. Ce cas fait ressortir la difficulté de diagnostiquer la blastomycose disséminée et établit le caractère endémique de la blastomycose dans le sud de la Saskatchewan.
MOTS-CLÉS : Blastomyces, blastomycose, infection fongique, Saskatchewan
1Department of Internal Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada; 2Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada; 3Department of Respirology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
Correspondence: Karen Bennie Ho, Internal Medicine, University of Saskatchewan, 1440-14 Avenue, Regina, Saskatchewan S4P 0W5 Canada. E-mail: [email protected]
Official Journal of the Association of Medical Microbiology and Infectious Disease Canada Journal officiel de l’Association pour la microbiologie médicale et l’infectiologie Canada
INTRODUCTION
Blastomycosis is a fungal infection caused by the dimorphic fungus Blastomyces dermatitidis. Blastomycosis can present with a wide variety of symptoms, with pulmonary infection being the most common. Extrapulmonary involvement via
hematogenous spread can affect almost every organ, includ- ing the skin, the genitourinary tract, joints, bones, and the central nervous system (1).
Diagnosis of blastomycosis is suggested when the char- acteristic round, multinucleated yeasts with broad-based budding are seen in fluid or tissue samples, but definitive
A case of disseminated blastomycosis
KB Ho, M Ng, K Tallon
10.3138/jammi.2019-0010 5 1
2020 5 1
Official Journal of the Association of Medical Microbiology and Infectious Disease Canada 5.1, 2020 doi:10.3138/jammi.2019-0010
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negative. An echocardiogram showed no evidence of vegeta- tion. Chlamydia trachomatis and Neisseria gonorrhoeae were not detected from a urine sample. Viral screens for human immunodeficiency virus (HIV), hepatitis B and hepatitis C, Epstein–Barr virus, and respiratory influenzae were negative. For autoimmune conditions, antinuclear antibody, rheuma- toid factor, uric acid, and a vasculitis panel were sent, and all returned normal.
With regard to malignancy screening, a CT abdomen scan did not reveal any lesions or masses. Protein electrophoresis did not reveal any Bence–Jones protein. Despite the lack of respiratory symptoms, without an obvious etiology to explain his fevers, a chest X-ray was performed. It showed a fine reticulonodular density throughout bilateral lungs. A  subsequent CT scan showed innumerable, diffuse, and ran- dom distribution of sub-2mm nodules. Differential diagnosis of such a radiographic pattern included miliary tuberculosis, viral infection, fungal infection, or hematogenous metastases.
Based on these findings, he was transferred to a tertiary centre for a bronchoscopy. Bronchoalveolar washings were lymphocytic predominant at 37%, with the lymphocytes being T cell dominant. Washings were negative for bacte- rial culture, acid-fast bacilli, viral serology, fungal culture, and galactomannan assay. Endobronchial biopsy results showed benign pulmonary tissues with small non-caseating granulomas. Grocott–Gomori methenamine silver (GMS), periodic acid–Schiff (PAS), and Ziehl–Neelsen (ZN) tissue stains were negative.
Attention was then focused on his left foot. An initial X-ray showed a subtle hypodensity on the dorsal aspect of the first tarsometatarsal articulation, and an MRI was recommended for further characterization. An MRI showed bone marrow edema and enhancement throughout the base and shaft of the first metatarsal, suggestive of osteomyelitis. Joint effusion was also seen, pointing to possible septic arthritis. He was taken to the operating room for joint aspiration and debridement. The joint aspirate culture unexpectedly grew budding yeast (Figure 1). After 1 week of incubation, B. dermatitidis was isolated with the use of a DNA probe. Samples from the tissue debridement also grew the same organism. With the diagnosis confirmed, and a history of prostatism, a urine fungal culture was sent; this also returned positive for B. dermatitidis after 1 week of incubation, establishing a fourth site of involvement.
The patient was initiated on itraconazole at 200 mg orally three times daily for 3 days, followed by 200 mg orally twice daily. At his most recent follow-up approximately 2 weeks post- discharge, he was tolerating his medication regimen well, with complete symptom resolution. A repeat chest X-ray showed resolution of the diffuse reticular pattern. Routine lab work showed that all inflammatory markers had normalized. He was continued on a regimen of itraconazole for a 6-month course.
diagnosis requires the isolation of B. dermatitidis in culture. Areas endemic to blastomycosis include the Mississippi and Ohio River valleys and Canadian provinces that border the Great Lakes and the St. Lawrence Seaway, including Manitoba, Ontario, and Québec (2–6).
We present a case of disseminated blastomycosis with pul- monary, osteoarticular, and genitourinary involvement. This case serves to highlight the clinical presentation of blastomy- cosis and its diagnostic challenges. As B. dermatitidis is not commonly recognized as endemic to southern Saskatchewan, this case also brings awareness to the prevalence of the fungal infection in this region.
CASE REPORT A 39-year-old man presented with a 1-week history of right hip pain, urinary hesitancy, and constitutional symptoms of intermittent fevers, night sweats, and rigours. Urinalysis showed microscopic hematuria but was negative for nitrites or leukocyte esterase. Urine bacterial culture was also negative. A computed tomography (CT) scan of the abdomen revealed a 7 mm non-obstructing kidney stone on the right, with no evidence of hydronephrosis or perinephric stranding. He was found to have an elevated prostate specific antigen (PSA) of 3.4 µg/L (normal 0.0–2.5 µg/L) and was given a 10-day course of ciprofloxacin for acute prostatitis. His symptoms improved while on antibiotic therapy. However, upon completing the antibiotic, his fever returned. He also developed a petechial rash over the dorsum of his left foot, which prompted him to return to his local hospital.
He denied any respiratory or gastrointestinal infectious symptoms. He endorsed urinary hesitancy, a weak stream, and the sensation of incomplete voiding, but denied any hematuria or dysuria. Besides the rash on his swollen left foot, he denied any other skin changes or arthralgia. He had no sick contact or recent travel history. His past medical history was only significant for a remote tonsillectomy and vasectomy. He did not take any prescription medication. He was a non-smoker and consumed minimal alcohol. His family history was significant for rheumatoid arthritis in his mother.
On initial presentation, he was febrile with a temperature of 39.0°C. On exam, he did not have any cervical lymphade- nopathy. Auscultation of the chest yielded clear breath sounds and normal heart sounds with no murmurs. His abdomen was benign, with no costovertebral angle tenderness. Examination of the extremities showed a non-blanchable petechial rash over the dorsum of his left foot, which was swollen and tender.
He had an elevated white blood cell count of 15,000 cells/ μL and a C-reactive protein (CRP) of 103.4 mg/L (normal CRP <10 mg/L). His electrolytes and creatinine were all within normal limits. Blood and urine bacterial cultures were
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A case of disseminated blastomycosis
DISCUSSION We presented a case of disseminated blastomycosis with pulmonary, osteoarticular, and genitourinary involvement. Blastomycosis is a fungal infection caused by the dimorphic fungus B. dermatitidis. Infection is through the inhalation of conidia that are present as mould in the environment. The conidia are subsequently transformed into yeast form in the human body (7). Risk factors for acquiring blastomy- cosis include immunosuppression (from collagen vascular disease or immunosuppressive medication) and exposure to soils in an endemic region (whether through occupation or recreation) (8,9). A recent review of blastomycosis cases in Northern Ontario found the majority of patients were males in the age group 30–39 years, consistent with this patient’s demographic (10). This patient’s pattern of symptoms was also compatible with disseminated blastomycosis. Nonetheless, it took more than 7 weeks from the onset of symptoms to arrive at the correct diagnosis. This serves to highlight the challenges in diagnosing this uncommon fungal infection.
The patient first presented with a fever of unknown origin (FUO). FUO is defined as a temperature higher than 38.3°C that persists for more than 3 weeks with no obvious source despite appropriate investigation (11). Differential diagnoses include infections (bacterial, viral, mycobacterial, and fungal), non-infectious inflammatory diseases, and malignancies (12). Initial investigative efforts were focused on bacterial infections. Nonetheless, initial blood and urine bacterial cultures were negative. An echocardiogram did not reveal any vegetation.
Furthermore, the patient did not improve after a course of antibiotics. The patient did not have risk factors for tuberculosis.
A screen for viral infections, autoimmune conditions, and malignancies also returned negative. The CT chest scan, showing a miliary pattern, was one of the first clues.
Typical radiographic findings of pulmonary blastomycosis include upper-lobe cavitary lesions and a mass-like infiltrate (1). A miliary pattern, such as the one seen in this patient, is much less common. Negative fungal cultures, PAS, and GMS stains from the bronchoscopy also complicated the diagnosis. Though a previous study reported high diagnostic yield for bronchoscopy samples in pulmonary blastomycosis (13), in this case, bron- chial washings were negative for fungal culture after 4 weeks of incubation. This could represent local control of disease. Despite findings on the CT chest, this patient did not endorse any respiratory symptoms. Bronchoalveolar washings showed a T-cell predominant population, which is necessary for control of disease (14,15). Endobronchial lung biopsy revealed non- caseating granulomas, a result of the host’s immune response. Taken together, it showed that a patient might be able to achieve local control even in disseminated disease. As a result, a nega- tive bronchoalveolar lavage and lung biopsy do not definitively rule out the presence of systemic B. dermatitidis.
This patient’s disseminated disease also involved his foot and prostate. Urinary obstruction secondary to prostatitis is a recognized manifestation of blastomycosis (16). It should be noted that the first two sets of urine culture returned negative. Even the final urine fungal culture that successfully isolated B. dermatiditis was initially reported as negative after 72 hours of incubation and an amendment had to be made several days later. Although the visualization of broad-based budding yeasts is commonly described in blastomycosis, morphological characteristics of fungi are often non-specific, and diagnosis by microscopy alone can be misguided (17). Isolation of the organism remains the definitive diagnostic method, though the longer incubation period of 1 to 4 weeks (18) certainly contributes to the diagnostic difficulties. Osteoarticular structures are also affected in approximately 25% of cases of disseminated blastomycosis (19). The vertebra and long bones are commonly affected sites (20), while involvement of the foot is rare. Even though the prostate, joints, and bones are known sites of involvement in disseminated blastomycosis, due to a low index of suspicion, the variability in clinical presentation, and the need for specific fungal cultures, estab- lishing a diagnosis can be extremely difficult.
Not recognizing a location as an endemic region also adds to the diagnostic challenge. Southern Saskatchewan is not traditionally recognized as a region endemic to blasto- mycosis, as endemic regions tend to border large bodies of water, with moderate temperatures and a humid environ- ment (18,21). Nonetheless, two recent case series suggested that B. dermatitidis may be endemic to Saskatchewan soils. A recent review documented 142 cases of canine and feline
Figure 1: Joint aspirate culture showing the characteristic broad-based budding yeasts of Blastomycoses
5.1, 2020 Journal officiel de l’Association pour la microbiologie médicale et l’infectiologie Canada 41
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KB Ho, M Ng, K Tallon
blastomycosis originating from Saskatchewan and Manitoba (22). Lohrenz et al (23) also reported on 13 cases of human blastomycosis in southern Saskatchewan, with most of the patients having no history of travel to known endemic areas.
Similarly, the patient in this case had no recent travel his- tory to endemic areas or known exposures, supporting the claim that B. dermatitidis is endemic to Saskatchewan. Health Canada reports an annual incidence rate of blastomycosis to be 0.62 cases per 100,000 people and includes Saskatchewan as a province of endemicity (24). Across Canada, the inci- dence of blastomycosis requiring hospitalization is 30 to 60 per 100,000 (24). Kenora, Ontario has the highest rate of hospitalizations, at 57.9 per 100,000 per year (10).
Timely and accurate diagnosis is of essence as disseminated blastomycosis can be fatal, with mortality reported to be 4%–6% (25). The majority of fatalities are due to the devel- opment of acute respiratory distress refractory to treatment (26,27). Management for mild to moderate disease favours the use of itraconazole (200 mg 3 times daily × 3 days, then 200 mg twice daily) (28). For severe acute illness, ampho- tericin B (3 to 5 mg/kg/d) is used (28). Fortunately, for this patient—even though he had disseminated disease involv- ing multiple organ systems—he achieved rapid resolution of his symptoms within 2 weeks of treatment. Duration of a complete treatment course is typically 6 to 12 months (28).
CONCLUSION We presented a case of disseminated blastomycosis in an immunocompetent patient, with pulmonary, genitourinary, and osteoarticular involvement. The unique presentation of his disease, the challenges associated with establishing a diagnosis, as well as under-recognition of southern Saskatchewan as an endemic region to Blastomyces all posed as obstacles in the investigation and management of this case. This case serves to remind us that regions endemic to blastomycosis may be broader than was previously thought, and include prairie provinces such as Saskatchewan. The greatest challenge in making the diagnosis of blastomycosis is considering it in the first place. As such, blastomycosis should be considered in patients who present with an FUO and objective findings in keeping with this fungal infection.
ACKNOWLEDGEMENTS: The authors would like to acknowledge Dr Kathy Malejczyk and the Microbiology Department of Reginal General Hospital for their assistance in obtaining images of the fungal smears.
COMPETING INTERESTS: The authors have nothing to disclose.
CONTRIBUTORS: Writing – Original Draft, KBH, MN; Writing – Review and Editing, KBH, MN, KT; Supervision, KT.
ETHICS APPROVAL: N/A
INFORMED CONSENT: N/A
ANIMAL STUDIES: N/A
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