Blastomycosis is a mycotic infection that typically affects the lung, but that can have dermatologic, orthopedic, genitourinary, and central nervous system manifestations. Blastomyces dermatitidis is a true human pathogen, which can produce disease in immunocompetent hosts. Risk factors for infection include residence in or travel to endemic areas and outdoor occupation, particularly those activities near open bodies of water and that disrupt soil. Immunosuppressed patients are also at increased risk for severe and disseminated disease. We present a case of a 79-year-old male who presented with a 2-week history of progressive right upper extremity weakness and severe odontogenic disease. He was found to have multiple brain abscesses with positive cultures from a cerebral abscess incision and drainage for B dermatitidis. He underwent an incision and drainage of the largest cerebral abscess and was treated with intravenous liposomal amphotericin B, which he tolerated poorly. He was subsequently switched to voriconazole, which was well tolerated, and his neurological deficits improved throughout his hospitalization.
Keywords: central nervous system blastomycosis, Blastomyces dermatitidis, intracranial mass, blastomycosis
Blastomycosis is frequently caused by inhalation exposure to aerosolized Blastomyces dermatitidis or Blastomyces gilcristi conidia following disruption of wet soil or organic matter, 1,2 although rare cases of traumatic inoculation (eg, accidental needle stick injury) have been reported. 2,3 Risk factors for infection are related to the likelihood of environmental exposure, including living in or travel to a known endemic region (eg, Great Lakes, Ohio and Mississippi River Valleys), particularly near open bodies of water, and outdoor activities. 2 A slight male preponderance has been noted, however this likely reflects an increased rate of participation in more exposure-risk activities rather than a true gender-specific risk. 2 Most patients with blastomycosis are immunocompetent, although immunosuppressed patients, particularly those with impaired cell-mediated immunity (eg, human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) and solid organ transplant), are at increased risk for severe and disseminated disease. 2,4
Primary infection predominately involves the lungs 5,6 with respiratory disease present in nearly 80% of cases. 2,3 Clinical symptoms are heterogeneous and nonspecific, ranging in severity from mild cough to acute respiratory failure, although subclinical infection can occur in nearly 50% of patients. 3 Extrapulmonary findings from hematogenous spread occur in 25% to 40% of symptomatic patients and can involve any organ system, although the most common sites are the skin, bones, genitourinary tract, and central nervous system (CNS). 2,3 Central nervous system involvement occurs in 5% to 10% of disseminated blastomycosis cases, 3,5 -8 with the majority of these patients also having active pulmonary or cutaneous involvement. 2 Isolated CNS blastomycosis is rare, with few case reports published. 9 Here, we present a case of a patient with isolated CNS blastomycosis including multiple brain abscesses presenting with focal neurologic deficits.
A 79-year-old Caucasian male presented to the emergency department with a several-week history of progressive right upper extremity weakness, dysarthria, and balance difficulties. He also had severe mandibular tooth pain over the preceding months. His past medical history was significant for noninsulin-dependent diabetes mellitus (NIDDM), chronic obstructive pulmonary disease (COPD) requiring nighttime supplemental oxygen, black lung disease, hypertension, and chronic diverticulitis. Notably, he had been on disability for more than 40 years after working as a coal miner. He currently worked as a preacher, lived in rural Kentucky, and often did work around his land. He often handled wild doves as a hobby, but did not care for any other animals. He did not reside near any construction or excavation sites and denied any recent travel. On admission, he was hypertensive (167/87 mm Hg), afebrile, had a normal heart rate, and with an oxygen saturation of 93% on room air. Significant physical examination findings included coarse breath sounds throughout all lung fields, 4/5 strength of the right upper extremity, right hemineglect, right apraxia, left facial droop, dysarthria with expressive aphasia, and increased left upper extremity tone. His dentition was poor and had more than 50% of his teeth missing with multiple dental caries. Labs demonstrated a leukocytosis (11.4 k/μL) with eosinophilia (2.03 k/μL), a normocytic anemia (13.4 g/dL), an elevated hemoglobin A1c (8.6%), an elevated erythrocyte sedimentation rate (27 mm/h), and an elevated C-reactive protein (1.5 mg/dL). Blood cultures were negative for growth of clinically relevant organisms. Testing for HIV and the viral hepatitis were negative.
Magnetic resonance imaging (MRI) with and without contrast of the brain revealed a 3 × 2.5 × 2 cm lesion in the left postcentral gyrus with thick, enhancing walls and a central area of restricted diffusion ( Figure 1 ), an 8 mm enhancing lesion in the right medial precentral gyrus and a 3 mm enhancing lesion in the right midcentral, precentral gyrus. A dental panoramic radiograph showed large periapical lucencies around the right mandibular canine with surrounding severe periodontal disease, consistent with abscesses. Chest radiographs were unremarkable, but computed tomography imaging of the lungs showed evidence of small chronic pulmonary emboli, hyperinflation with air trapping, chronic bronchitis, and emphysema-related changes. The patient was started on empiric intravenous vancomycin, ceftriaxone, and metronidazole to cover for gram-positive cocci, gram-negative rods, and anaerobes.
(Left) An axial T1-weighted magnetic resonance image postcontrast showing the thick wall with surrounding edema of the abscess in the left postcentral gyrus. An area of restricted diffusion is seen on diffusion-weighted imaging, which is consistent with an abscess (right).
Neurosurgery performed a craniotomy with incision and drainage (I&D) of the left postcentral gyrus abscess on day 2 of admission. During this time, his remaining teeth were extracted by oral/maxillofacial surgery. Mycological tissue culture of the brain abscess was positive for Blastomyces dermatitidis (B dermatitidis) on day 8 of culture (admission day 9; Figures 2 and and3). 3 ). There were no other source or sites of infection discovered other than the brain abscesses. No cultures of the oral abscesses were taken, and subsequent serum bacterial and mycologic blood cultures were unremarkable. Fungal serologies were negative for all analytes, including blastomyces, aspergillus, histoplasma, and coccidioides. Following identification of the B dermatitidis, his antibiotics were changed to intravenous liposomal amphotericin B, dosed at 5 mg/kg and administered once daily as per the Infectious Diseases Society of America guidelines. 10 However, he experienced rigors and worsening renal function following one dose of the drug’s administration, leading to substituting the amphotericin B for voriconazole. The voriconazole was dosed at 6 mg/kg and administered twice daily for a planned treatment course of 12 months. It was well-tolerated and he had noticeable improvement in his speech and motor function within the first few days to weeks after starting treatment. A repeat MRI obtained two and a half months after his initial MRI showed a decrease in size of the residual left parietal abscess and right frontal microabscesses ( Figure 4 ). At his last follow-up he had been progressing well at his rehabilitation facility with improvement in ambulation, though patient still had significant weakness of the right upper extremity. He was also transitioned to fluconazole from voriconazole due to concerns of adverse effects from his primary care provider with the goal of 6 months of continued therapy.
Blastomyces dermatitidis colony morphology at 25°C incubation (room temperature), 2 weeks: Pinpoint colonies are usually first detected days to weeks after initial plating of the specimen(s). Blastomycoses dermatitidis is dimorphic, with slow-growing, fluffy, white colonies and fine tan-white aerial mycelium (mold phase) seen after room temperature incubation, and growing as a yeast in 37 ° C. Probe identification is possible after adequate growth (left: Brain heart infusion with blood agar; right: Inhibitory mold agar).
Blastomyces dermatitidis microscopic findings: Blastomyces dermatitidis’ filamentous growth (mold phase) has septate hyaline mycelium that produce small, smooth, and oval-round microconidia approximately 1 μM in diameter. Microconidia are located at the terminal ends of short lateral conidiophores, giving the organism its characteristic “lollipop-on-a-stick” morphology. (Lactophenol cotton blue stain, 400×).
(Left) repeat axial T1-weighted magnetic resonance image postcontrast obtained 2.5 months after the original magnetic resonance imaging showing postsurgical changes and decrease in size of original abscess. An area of restricted diffusion is again noted on diffusion weighted imaging (Right), which is consistent with an abscess.
We presented a case of a 79-year-old male with a history of COPD, black lung disease, and poorly-controlled NIDDM who presented with focal neurological deficits. He was found to have isolated CNS blastomycosis with multiple brain abscesses and was treated with an I&D of his largest abscess, then with intravenous liposomal amphotericin B. He experienced complications from this antifungal regimen, so was switched to voriconazole with improvement in his neurological manifestations throughout his treatment course.
The incidence of isolated CNS blastomycosis is limited to case reports 9 ; however, a case series of 22 patients found that 5 (22.7%) of them had only CNS blastomycosis, but the authors felt that concomitant infection at other sites was possibly overlooked. 11 Central nervous system blastomycosis may present as intracranial or spinal abscesses, leptomeningitis, or encephalitis, 7,8,11 and tends to involve the cerebellum. 9,12 Symptoms are often nonspecific and can range from headache, focal neurologic deficits, encephalopathy, vision changes, seizure, and rarely meningismus with associated meninigitis. 12 Central nervous system involvement is almost invariably the result of hematogenous spread from a primary pulmonary infection 2,13 and is estimated to occur in approximately 5% to 10% of cases of systemic blastomycosis, although an older autopsy series suggest that this could be as high as 33%. 14 In our case, this patient presented with focal neurologic deficits and had isolated CNS blastomycosis without clear concurrent pulmonary or skin involvement (the most common sites for primary disease). Other than his dental abscesses, no other potential source of infection was discovered. It is suspected that his dental caries were the likely source of his infection because the location of his brain abscesses (mostly in the frontal lobe) is consistent with a contiguous spread from the oral cavity in cases of bacterial brain abscesses. 15 However, this assumption cannot be definitively confirmed because cultures were not obtained from the dental extractions and only obtained from the I&D of his CNS abscess. Notably, however, there have been multiple reports in the literature of disseminated disease arising from maxillary/mandibular blastomycosis mimicking bacterial dental abscesses. 16
Mycologic culture is the gold standard for the diagnosis of blastomycosis; however, negative cerebrospinal fluid cultures and/or antigen testing does not necessarily exclude infection. 8 The sensitivity of serum antigen testing is reported as 89% in disseminated blastomycosis with a specificity of 79%. 17 However, the antigens do cross-react with other endemic mycosis resulting in false-positive results. 17 Similarly, negative serologic testing and/or blood cultures do not definitively exclude disease. 8 Serologic testing is not useful for the diagnosis of blastomycosis due to its cross-reactivity with other endemic mycosis and low sensitivity (ranging from 28% to 64%). 18 -20 Some patients with CNS blastomycosis require a tissue biopsy with subsequent histopathologic examination to identify the organism’s presence. 2,7 In our case, Blastomyces antibodies were negative and the patient was diagnosed from mycological tissue culture of the brain abscess.
The prognosis of CNS blastomycosis is unknown due to its rarity, however for blastomycosis, the mortality rate based on surveillance data has been reported as being between 4% and 22%. 21 -23 In these studies, higher rates of mortality were seen among blacks, elderly (≥65 years of age), males, and those with a delayed diagnosis (≥128 days after symptom onset) and treatment with appropriate antifungal therapy. 21 -23 In our case, he was an elderly male, which put him at a worse prognosis; however, he presented within a few weeks of symptom onset.
Current guidelines for the treatment of CNS blastomycosis is 4 to 6 weeks of intravenous amphotericin B, preferably the liposomal formulation, followed by at least 12 months of oral azole therapy. 3,24 Liposomal amphotericin B is preferred because of its increased CNS penetration with lower rates of nephrotoxicity versus other formulations. 3,25 Infectious Diseases Society of America guidelines do not favor any specific azole antifungal therapy (fluconazole, itraconazole, voriconazole) for CNS blastomycosis; however, voriconazole has demonstrated a desirable combination of adequate CNS penetration and antifungal activity in published cases. 10,26 In our case, he was treated with intravenous liposomal amphotericin B, but experienced rigors and an acute kidney injury. He was then switched to voriconazole with improvement in his neurological manifestations throughout his hospitalization.
Overall, it is important to recognize that infectious processes of the CNS can present with focal neurological deficits. Blastomycosis most commonly affects the lung, but can rarely present as isolated CNS abscesses. Risk factors include environmental exposure and immunosuppression, but most patients are immunocompetent. Symptoms for CNS blastomycosis are nonspecific. The treatment includes intravenous amphotericin B for 4 to 6 weeks, followed by at least 12 months of an oral azole.
Authors’ Note: Informed consent was obtained from the patient. Alexander J. Fenwick is currently affiliated with the Department of Pathology, Division of Microbiology at The Johns Hopkins University School of Medicine.
Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding: The authors received no financial support for the research, authorship, and/or publication of this article.
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