Case Presentation: A 23-year-old male with a history of migraines and a renal transplant presented to the ED with diffuse headaches and photophobia. He was treated with Ganciclovir and Doxycycline for positive HHV6 and Lyme disease, respectively. His MRI was negative for intracranial abnormalities but, CSF showed elevated protein and glucose. A repeat LP a week later was positive for Histoplasmosis and the patient was started on IV Amphotericin B and Voriconazole. A repeat MRI during the same admission showed multifocal leptomeningeal hyperenhancements compatible with meningitis. Despite negative Meningitis/encephalitis panel, fungal cultures, and urine histoplasma/blastomyces, his CSF protein, glucose, and nucleated cell count remained abnormal. A CT chest showed left lower lobe foci of clustered nodularity consistent with an infection, but a subsequent bronchoalveolar lavage was negative for any fungi. A few days later, his Blastomyces antigen and antibody were positive, and he maintained Ampho B/Vori treatment. The patient was discharged on his regular home medications and oral Voriconazole. Given the patient’s kidney transplant history, immunosuppression, and the potential for nephrotoxicity associated with Voriconazole, both Tacrolimus and Voriconazole levels were adjusted and checked weekly to maintain therapeutic indices and prevent adverse effects.

Discussion: Histoplasmosis and Blastomycosis are fungal infections that can manifest in organ transplant recipients due to environmental mold exposure, reactivation of a latent infection, or transmission from the donor [2]. These infections are endemic to the Midwest region of North America and typically present with pulmonary involvement [3,4] yet our patient presented with an uncommon manifestation of CNS involvement, portrayed by headaches and focal neurological deficits [5]. Although this patient’s transplant elevates his risk of contracting histoplasmosis and Blastomycosis, these infections remain uncommon in solid organ transplant recipients, with an incidence of ≤1% [6,7]. Rather, our patient’s geographic location in an endemic region puts him at a higher risk for obtaining these infections. The patient’s transplant in 2014 deviates from the median occurrence of 6 months post-transplantation for Blastomycoses, with a range extending to five years [2]. Histoplasmosis exhibits a bimodal pattern of infection, with 40% of infections within the initial 6 months following transplantation, and 34% reported between 2-11 years post-transplant [8]. Fungal culture isolation remains the standard diagnostic approach for Histoplasmosis and Blastomycosis [3,4] but its sensitivity may be limited in cases involving CNS involvement, as in our patient. In most cases, pulmonary involvement requires a biopsy and histological exam for confirmation. However, our patient’s bronchoalveolar lavage showed no evidence of pulmonary fungal infection, eliminating the need for a lung biopsy.

Conclusions: This case highlights an uncommon CNS presentation of Histoplasmosis and Blastomycosis in a patient with a history of solid organ transplant. Despite these infections being rare, the patient’s geographic location and immunocompromised state increased his susceptibility. Early diagnosis and at least a 1-year treatment with anti-fungals [9] are crucial for managing these infections in transplant patients. Further research on CNS histoplasmosis is needed to elucidate the proper approach to diagnosis and treatment in this patient population [10]