First reported Rhodotorula mucilaginosa brain abscess: Found as coinfection in woman with common variable immune deficiency

Key Clinical Message Rhodotorula is a rare pathogen seen in the immunocompromised host; while cases of Rhodotorula meningitis have been reported, there are no published cases of Rhodotorula brain abscess. We describe the diagnosis and management of a woman with common variable immune deficiency presenting with concomitant Rhodotorula and Nocardia brain abscesses.


| INTRODUCTION
Rhodotorula, a pink to red-pigmented yeast in the family Sporidiobolaceae, is considered a ubiquitous commensal organism.Previously, Rhodotorula was not considered a human pathogen, but with the increasing prevalence of infectious niduses (e.g., central venous catheters), Rhodotorula has since emerged as a cause of opportunistic infection with a prevalence between 0.5% and 2.3% among patients with fungemia. 1,2Limited data suggests the disease mostly spreads from an infectious source to its destination through central vasculature; peripheral cultures may be falsely negative. 3Previous reports of Rhodotorula infections have included sepsis, pneumonia, meningitis and endocarditis, typically in immunocompromised hosts. 3,46][7] Here, we describe a case of a 40-year-old Caucasian woman with common variable immune deficiency (CVID) and brain abscesses due to both Rhodotorula mucilaginosa and Nocardia abscessus.

| CASE HISTORY AND EXAMINATION
A 40-year-old Caucasian woman presented to the emergency department complaining of fevers, worsening shortness of breath, and new-onset witnessed tonicclonic seizures.Her medical history was significant for mental retardation, tobacco usage of 40 pack years, chronic obstructive pulmonary disease diagnosed in her 30s with a 2 L O2 home oxygen requirement, and multiple complicated previous hospitalizations for various infections.She also endorsed 2 months of unwitnessed syncopal episodes, headaches with intense pain over the left eye, worsening dyspnea with exertion (able to walk 15 feet from a baseline of 100), cough producing yellow sputum, and weight loss.She had no associated photophobia, neck rigidity, or blurred vision.On physical exam, she was febrile to 103°F, tachycardic, and hypoxemic despite home oxygen support.She had diffuse crackles throughout both lung fields; subsequent chest x-ray showed expanded lung fields consistent with the patient's known COPD, and a diffuse reticulonodular infiltrate suggested by CT scan to be necrotizing pneumonia with cavitation.Brain MRI revealed multiple scattered intra-axial ring-enhancing lesions in the left posterior frontal lobe, left posterior parietal lobe, right occipital lobe and left temporal lobe, all with restricted diffusion, and surrounding edema (Figure 1).

INVESTIGATIONS, AND TREATMENT
Given these findings, empiric antibiotic treatment was started for suspected brain abscess, but as metastatic disease could not be ruled out, brain, and transbronchial biopsies were performed.Histopathologic examination revealed a brain abscess with both budding yeast and filamentous bacilli (Figure 2), and cultures of the brain biopsy grew R. mucilaginosa and N. abscessus.Lung biopsy was unremarkable.Due to the rare, invasive fungal infection in the absence of known risk factors such as CVC, workup for immunocompromising conditions was undertaken, aspects of which are presented in Table 1.
This workup eventually revealed a diagnosis of CVID.Empiric antibiotic therapy was thus replaced with meropenem, trimethoprim-sulfamethoxazole, and liposomal amphotericin B. Amphotericin B associated electrolyte abnormalities prompted a switch to voriconazole, but unfortunately, despite several weeks of intensive medical therapy, the patient's respiratory status continued to decline, and she was transferred to the ICU for mechanical ventilation.

| OUTCOME AND FOLLOW-UP
After 2 weeks, the patient was still dependent upon mechanical ventilation and prognosis was felt to be poor.Tracheostomy was discussed with the patient's power of attorney, but after continued deterioration, comfort measures were prioritized, and the patient passed.

| DISCUSSION
Rhodotorula remains a rare cause of infection.][10][11] As it is still not clear why some immunocompromised patients develop complications such as Rhodotorula meningitis or endocarditis whereas others simply have fungemia, patient history, and clinical presentation alone may not converge on Rhodotorula. 12,13Thus, histopathologic evaluation remains essential to confirming diagnosis and, as in this case, determining treatment course.There remains no definitive treatment algorithm for Rhodotorula: suggested treatments include simple supportive care, fluconazole, various formulations and dosing regimens of amphotericin B with or without flucytosine, and flucytosine/itraconazole combinations. 14,15As seen in patient, these regimens often cause complications due to their toxicities.Additionally, this patient's comorbidities, especially her coexisting respiratory failure, were felt to have contributed to her poor outcome.We hope the contribution of this novel manifestation of Rhodotorula as causing brain abscesses nonetheless serves as another datapoint to hopefully improving the diagnosis and management of this rare disease.

F I G U R E 1
Brain MRI demonstrated intra-axial ring-enhancing lesions in the left posterior frontal lobe, left posterior parietal lobe, right occipital lobe and left temporal lobe, all with restricted diffusion and surrounding edema.
T A B L E 1The diagnostic workup leading to a diagnosis of CVID included multiple HIV tests, which were consistently negative, titers that remained low despite vaccinations, a positive mitogen induced lymphocyte blastogenesis test, and negative purine nucleoside phosphorylase and adenosine deaminase tests.Based on the patient's hypogammaglobulinemia, impaired antibody response, negative HIV test, and mitogen tests, the patient was believed to have common variable immune deficiency.curation