Pneumonia, Septic Arthritis, and Brain Abscesses in a Construction Worker

(See pages 1684–5 for the Photo Quiz.) Diagnosis: Disseminated Blastomyces dermatitidis. The right-toe specimen showed a thick-walled organism with single broad-based budding; Blastomyces dermatitidis was suspected (Figure 2) and later confirmed by DNA probe identification at the mycobacterial/nocardia research lab at the University of Texas Health Center at Tyler. The patient's poor performance despite broad-spectrum antibiotics had prompted empiric treatment with voriconazole 6 mg/kg every 12 hours several days prior, but when blastomycosis was suspected, the antifungal was changed to liposomal amphotericin B, 5 mg/kg every 24 hours. The patient's sputum, bronchoalveolar lavage fluid, and lung biopsy also revealed B. dermatitidis. Liposomal amphotericin B is the drug of choice for central nervous system (CNS) or life-threatening disease [1, 2]. Lipid preparations of amphotericin B are effective in animal models of blastomycosis, but they have not been studied in controlled trials involving humans. However, clinical experience indicates that the lipid formulations should be equally as efficacious as the deoxycholate formulation and are associated with less toxicity [2]. Our patient was treated with liposomal amphotericin B, but after 2 weeks of effective therapy with only minimal improvement, the patient underwent a brain biopsy (Figure 3) of the ring enhancing lesions (Figure 1) to rule out coexisting pathogens; however, the biopsy was consistent with B. dermatitidis by culture and DNA probe. He had a slow response to standard therapy with liposomal amphotericin B, which was concerning and prompted the addition of voriconazole. Renal insufficiency developed; therefore, a switch to amphotericin B deoxycholate was not ideal. Voriconazole has been used successfully in immunosuppressed patients and patients with CNS disease due to its ability to achieve high concentrations in the brain and cerebrospinal fluid [3, 4]; however, it is not recommended as first-line therapy for CNS/life-threatening disease, but rather as step-down therapy following initial amphotericin treatment for 1–2 weeks or until clinical improvement [2]. Therefore, we opted to use combination therapy with liposomal amphotericin B and voriconazole. The patient improved and he was discharged to rehabilitation after a total of 6 weeks in the hospital. Brain T1-weighted magnetic resonance imaging postcontrast with ring-enhancing lesions in cerebellum. Blastomyces dermatitidis shown by lacto phenol cotton blue stain in yeast form with thick cell wall and broad-based budding (×100 magnification). Brain biopsy, showing Gomori methenamine silver stain enhancing the numerous nonencapsulated fungal yeast forms with double-contoured refractile wall. Blastomyces dermatitidis is a dimorphic fungus endemic in North America in the southeastern and south-central states, especially those bordering the Mississippi and Ohio river basins. It is also found in the Midwestern states and Canadian provinces bordering the Great Lakes, as well as in a small area in New York and Canada along the St Lawrence River [5]. Our patient might have acquired the infection while doing construction work in B. dermatitidis–endemic areas. Blastomyces dermatitidis causes systemic pyogranulomatous disease. The usual portal of entry is the lungs [6], and disease at other body sites is the result of disseminated infection [5]. Extrapulmonary disease is found in 25%–40% [7–9] of patients, and skin, bones, and genitourinary system are the most frequent sites. CNS involvement is rare in immunocompetent hosts and has been reported in <5% of cases [5]. Blastomyces dermatitidis exhibits thermal dimorphism by growing in culture at 25°C–28°C as a mold and at 37°C as yeast. The yeast varies in size from 5 µm to 15 µm, larger than Histoplasma (2–5 µm). The yeast is round and has a double cell wall appearance, and budding occurs along a broad base where the daughter cell becomes as large as the mother cell before detaching (Figure 2). This feature distinguishes Blastomyces from similar yeast cells, such as Cryptococcus and Paracoccidioides [10]. Acknowledgments. We thank the Tufts Medical Center microbiology department, especially Eunice Charles and Ruth Adams, as well as the pathology department, especially Dr Barbara Weinstein, for assistance with photography and with the microbiological and pathological evaluation of our patient's case. Potential conflicts of interest. All authors: No potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

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