Case Presentation: A 58-year-old immunocompetent male with type 2 diabetes, hypertension, and dyslipidemia presented with four days of sharp right-sided headache associated with nausea, vomiting, and disequilibrium. He endorsed a chronic cough for several months but denied recent fevers, weight loss, or international travel. Examination revealed a wide-based waddling gait. CT head showed bilateral cerebellar edema with fourth-ventricle effacement and minimal inferior descent of the cerebellar tonsils. MRI revealed multiple ring-enhancing lesions with vasogenic edema, mass effect, and mild to moderate ventriculomegaly, concerning for metastasis versus atypical infection. Empiric ceftriaxone, vancomycin, and fluconazole were initiated. CT chest revealed a 2.5 cm spiculated left perihilar lung lesion with mediastinal lymphadenopathy, suspicious for primary lung malignancy. Bronchoscopic biopsy revealed a hyalinized, noncaseating granuloma, thus rheumatology found low concern for sarcoidosis. Initial broad infectious workup (cryptococcal antigen, toxoplasma serologies, Quantiferon Gold, galactomannan, histoplasma antigen) was negative. Neurosurgery deferred brain biopsy due to a stable neurologic exam. Final fungal culture from the lung biopsy speciated Blastomyces dermatitidis, confirming disseminated blastomycosis with CNS involvement. The patient began liposomal amphotericin B, transitioned to isavuconazole after renal toxicity, and started dexamethasone for cerebral edema. He was discharged on oral isavuconazole and dexamethasone, with follow-up arranged with Infectious Disease, Neurology, and Neuroimmunology.
Discussion: Blastomyces dermatitidis is a dimorphic fungus causing systemic pyogranulomatous infection, with CNS disease in only 5-10% of disseminated cases.1 CNS disease may appear as meningitis, abscesses, or mass lesions, often mimicking malignancy or sarcoidosis, leading to diagnostic delay. This case displays several diagnostic challenges: radiologic resemblance to cerebellar metastases, nondiagnostic granulomatous biopsy, and negative initial infectious workup. Urine Histoplasma antigen, often used due to cross-reactivity with Blastomyces, was negative, highlighting its limited sensitivity. Culture provided definitive diagnosis. Amphotericin B is first-line for CNS disease, but nephrotoxicity required transition to isavuconazole. Though evidence is limited, isavuconazole’s CNS penetration and tolerability make it a viable alternative.2 Clinicians should maintain suspicion for endemic fungi when evaluating CNS lesions, even in immunocompetent patients. Exposure history is key: while this patient denied international travel, he resided in Chicago, a known endemic region.3 Early multidisciplinary collaboration was essential to diagnosis and management.
Conclusions: Disseminated blastomycosis with CNS involvement is rare, particularly in immunocompetent patients, and may mimic malignancy or sarcoidosis. Diagnosis often requires tissue biopsy and culture, as initial pathology may be nonspecific. Our case highlights the critical role of broad differential consideration, multidisciplinary evaluation, and early antifungal therapy to optimize outcomes.