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\begin{document}

\title{First Reported Rhodotorula mucilaginosa Brain Abscess: Found As
Coinfection in Woman with Common Variable Immune Deficiency}



\author[1]{Arjun Bhatt}%
\author[2]{Melinda Dunalp}%
\author[2]{Pham Han}%
\author[2]{Kimmo Hatanpaa}%
\author[3]{Philipp Boyer}%
\author[2]{Rita Gander}%
\author[3]{Anna Symmes}%
\affil[1]{Brody School of Medicine at East Carolina University}%
\affil[2]{UT Southwestern}%
\affil[3]{East Carolina University}%


\vspace{-1em}



  
  \date{May 25, 2024}


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\textbf{First Reported \emph{Rhodotorula mucilaginosa} Brain Abscess:
Found} \textbf{As Coinfection} \textbf{in Woman with Common Variable
Immune Deficiency}

\textbf{Authors:} Arjun Bhatt, B.A.\textsuperscript{1}

Melinda S. Dunlap, M.D.\textsuperscript{2}

Han Pham, M.D.\textsuperscript{3}

Kimmo J. Hatanpaa, M.D., Ph.D\textsuperscript{3}

Philip Boyer, M.D., Ph.D\textsuperscript{3}

Rita M. Gander, Ph.D\textsuperscript{3}

Anna G. Symmes, M.D.\textsuperscript{1}

\textbf{Affiliations:} Department of Internal
Medicine\textsuperscript{1}

Brody School of Medicine

Greenville, North Carolina

Departments of Internal Medicine\textsuperscript{2} and
Pathology\textsuperscript{3}

University of Texas Southwestern Medical Center

Dallas, Texas

\textbf{Correspondence:}

Anna G. Symmes, M.D.

ECU Health Medical Center

Department of Internal Medicine

2100 Stantonsburg Road

Greenville, NC 27519

Phone: 252-847-4100

Email: symmesa21@ecu.edu

\textbf{Key words:} \emph{Rhodotorula, Nocardia} , CVID, brain abscess

\textbf{Running Title:} \emph{Rhodotorula} Brain Abscess As
Co-infection\textbf{Conflict of Interest Statement:} All authors declare
that they have no conflicts of interest.

\textbf{Consent Statement:} Written informed consent was obtained from
the patient to publish this report in accordance with the journal's
patient consent policy.

\textbf{Key Clinical Message:}

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

\textbf{Introduction:}

\emph{Rhodotorula} , a pink to red-pigmented yeast in the
family\emph{Sporidiobolaceae,} is considered a ubiquitous commensal
organism. Previously, \emph{Rhodotorula} was not considered a human
pathogen, but with the increasing prevalence of infectious niduses (e.g.
central venous catheters), \emph{Rhodotorula} has since emerged as a
cause of opportunistic infection {[}1{]}. Previous reports of
\emph{Rhodotorula}infections have included sepsis, pneumonia, meningitis
and endocarditis, typically in immunocompromised hosts. To our
knowledge, no case of Rhodotorula brain abscess in either an
immunocompetent or immunocompromised host has yet been reported
{[}1-4{]}. Here, we describe a case of a 40-year-old Caucasian woman
with common variable immune deficiency (CVID) and brain abscesses due to
both\emph{Rhodotorula mucilaginosa} and \emph{Nocardia abscessus} .

\textbf{Case History \& Examination:}

A 40-year-old Caucasian woman presented to the emergency department
complaining of fevers, worsening shortness of breath, and new-onset
witnessed tonic-clonic 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 2L O2 home oxygen
requirement, and multiple complicated previous hospitalizations for
various infections. She also endorsed two 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\selectlanguage{ngerman}ºF, 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 (Fig 2).

\textbf{Differential Diagnosis, 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 1), and cultures of the brain biopsy
grew\emph{R. mucilaginosa} and \emph{N. abscessus} . Lung biopsy was
unremarkable. Due to the rare, invasive fungal infection in the absence
of known risk factors such as CVC, work-up for immunocompromising
conditions was undertaken, eventually revealing 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.

\textbf{Outcome and Follow-up}

After two 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.

\textbf{Discussion:}

\emph{Rhodotorula} remains a rare cause of infection. Previous reports
of disease caused by \emph{Rhodotorula} have primarily been found in
immunocompromised hosts---~such as the patient presented here with CVID
--- with a majority of these involving CVC - associated infections. As
it is still not clear why some immunocompromised patients develop
complications such as \emph{Rhodotorula} meningitis or endocarditis
whereas others simply have fungemia, patient history and clinical
presentation alone may not converge on \emph{Rhodotorula} . Thus,
histopathologic evaluation remains essential to confirming diagnosis
and, as in this case, determining treatment course. There remains no
definitive treatment algorithm for \emph{Rhodotorula} : suggested
treatments include simple supportive care, fluconazole, various
formulations and dosing regimens of amphotericin B, and
flucytosine/itraconazole combinations. As seen in our 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\emph{Rhodotorula} as causing brain abscesses nonetheless serves as
another datapoint to hopefully improving the diagnosis and management of
this rare disease.

\textbf{Acknowledgements}

We thank Deanna A. Sutton, Ph.D for reviewing the stained slides, Sanjay
Revankar, M.D. for reviewing the manuscript and Bobbie Wortham for
administrative assistance in manuscript preparation.

\textbf{Author Contributions}

\emph{Arjun Bhatt, BA} : Wrote first draft of manuscript, implemented
suggested edits, and coordinated team.

\emph{Melinda S. Dunlap, M.D.} : Direct patient care.

\emph{Han Pham, M.D.} : Direct patient care.

\emph{Kimmo J. Hatanpaa, M.D., Ph.D} : Performed histopathological
analysis \& made critical diagnosis. Helped edit manuscript.

\emph{Philip Boyer, M.D., Ph.D} : Consulting pathologist. Helped make
diagnosis.

\emph{Rita M. Gander, Ph.D} : Manuscript editing, figure curation.

\emph{Anna G. Symmes, M.D.} : Manuscript editing.

\textbf{References}

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MA, Stamatelopoulos S. \emph{Rhodotorula} septicemia: case report and
minireview. Clin Microbiol Infect \textbf{2001} ; 7:100-2.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

\textbf{Figure 1}

Histologic evaluation of brain tissue identified : A) abundant necrotic
debris and a chronic inflammatory cell infiltrate admixed with fungal
forms (thin arrow) and filamentous bacteria (thick arrows) within the
parenchyma (Gomori's methenamine silver (GMS) stain; 400 x
magnification); B) On higher magnification, hyphal forms with globose
yeast cells (Periodic acid-Schiff stain; 1,000 x oil magnification) and
C) beaded, branching filamentous bacteria were seen (GMS; 1,000 x oil
magnification).\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

\end{center}
\end{figure}

s

Figure 2: 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.

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