Case Presentation
This is the case of a 44-year-old woman who initially presented in
August 2020 for evaluation of worsening dyspnea and bilateral lower
extremity swelling for two weeks. She also complained of unintentional
weight loss of about 7.3 kilograms (16 pounds) in the preceding three
months. The patient reported a remote history of intravenous opioid
abuse; she quit seven years before and was enrolled in a methadone
program for recovery. She also had a long-standing history of asthma and
chronic Hepatitis C infection with unsuccessful treatment twenty years
ago due to medication intolerance. At the time of her presentation, her
vitals were significant for tachycardia of 113 beats per mins and a
low-grade fever of 99.7F. Her physical examination revealed a distended
abdomen, marked splenomegaly, and bilateral lower extremity pitting
edema. Heart and lung sounds were normal, with normal jugular venous
pressure, no pericardial friction rub, and no stigmata of endocarditis.
Her laboratory reports revealed pancytopenia, elevated transaminase
levels, elevated creatinine suggestive of acute kidney injury, and a
deranged coagulation profile. The Hepatitis C antibody tested was
positive, however, the Hepatitis C quantitative polymerase chain
reaction for ribonucleic acid was negative. Human Immunodeficiency Virus
(HIV) testing and other serologies were negative.
Ultrasound Duplex doppler of the lower extremities bilaterally were
negative for deep vein thromboses. Computed tomography (CT) of the
abdomen and pelvis and CT angiogram with pulmonary embolism protocol on
her presentation ruled out pulmonary embolism and were significant for
two small nodules on the liver (likely hemangiomas), severe splenomegaly
with several non-specific splenic nodules and mild dilatation of the
biliary tree. She was admitted for further evaluation and management.
During the initial days of her admission, blood cultures taken on her
presentation were found to be positive for Candida parapsilosis,and she was started on liposomal Amphotericin B and fluconazole (seeTable 2 for sensitivity results of the organism). A 2-D
transthoracic echo revealed a large vegetation on the left aortic cusp
protruding into the left ventricular outflow tract. A transesophageal
echocardiogram (TEE) confirmed it to be an 11 x 4 mm soft tissue mobile
mass on the ventricular surface of the left coronary cusp of the aortic
valve (Figure 1) . She remained persistently pancytopenic during
her admission, and a bone marrow biopsy done for further evaluation
revealed a monocellular bone marrow with trilineage hematopoiesis and
megakaryocytic atypia.
Her cultures remained positive for C. parapsilosis for four weeks
despite maximal therapy with different antifungals, limited by her
underlying liver disease (Child-Pugh class B), including caspofungin and
micafungin. A repeat TEE showed an increase in the size of vegetation to
11 x 16 mm. Due to the absence of concrete clinical trial data, it was
difficult to frame a definitive therapeutic strategy, especially the
need for valvular surgery. Based on the recommendations of published
observational studies, she ultimately had an aortic valve replacement
with a number 23 bovine Edwards aortic valve studies after clearing her
fungemia. Cultures of the valve taken during the procedure were positive
for Candida parapsilosis . Her post-operative stay was complicated
by recurrent atrial flutter with a 4:1 atrioventricular block, which was
adequately ablated, and she was subsequently started on anticoagulation.
She received six weeks of antifungal therapy post-procedure with
intravenous micafungin, after which her blood cultures remained negative
for fungal growth. She was eventually discharged home on oral
fluconazole for three to six months with outpatient follow-up. However,
she was non-compliant with therapy and non-compliant with follow-up.
In November 2022, she returned to the emergency department with a
three-day history of sudden onset, constant, severe left upper quadrant
pain associated with multiple episodes of non-bilious, non-bloody
emesis. She denied fever, chills, diarrhea, constipation, hematemesis,
hematochezia, bloating, or abdominal distension. She also reported poor
oral intake and a decreased appetite. Vitals included a blood pressure
of 138/91 mmHg, a pulse rate of 88 beats per minute, a respiratory rate
of 18 per minute, a temperature of 97.8 F, and oxygen saturation of 97%
at room air. Her physical exam was significant for left upper quadrant
tenderness without clinical features of localized or generalized
peritonitis. Other aspects of the physical exam were within normal
limits. Her initial laboratory investigations were significant for mild
normocytic anemia, leucopenia, elevated aspartate and alanine
aminotransferases, and alkaline phosphatase (Table 1 ).
A chest radiograph cleared the chest for any significant infiltrates. A
right upper quadrant ultrasound scan was significant for a benign, small
liver hemangioma with no evidence of gallstones and a normal common bile
duct. A computed tomography (CT) of the abdomen and pelvis was
significant for splenomegaly with a large splenic infarct, a dilated
splenic vein, two small hemangiomas within the liver, and a right
ovarian cyst (Figure 2 ). Given her prior history of
endocarditis with aortic valvular repair and a new finding of splenic
infarction, there was a high clinical suspicion of endocarditis, and
blood cultures were sent on admission, and an echocardiogram was
ordered. A 2-D transthoracic echocardiogram showed no valvular
vegetation, no regional wall motion abnormalities, and a normal left
ventricular ejection fraction of 60–65%. Blood cultures taken on
admission were negative for two days. The patient had resolution of her
left lower quadrant pain and vomiting, remained afebrile with a normal
white cell count, and was discharged to follow-up outpatient with
cardiology for a transesophageal echocardiogram in the next three days,
follow-up with hematology for hypercoagulable workup, and follow-up with
infectious diseases. One day after discharge, blood culture resulted
positive for the growth Candida species at three days. The patient was
called and readmitted to the hospital, where she was started on
antifungal therapy with caspofungin. Beta-D glucan was noted to be more
than 500 pg/nl. The Candida species was later identified again asCandida parapsilosis . Transesophageal echocardiography
demonstrated a bioprosthetic aortic valve with normal movement and a 5mm
x 5mm nodular thickening of the right coronary cusp with no definitive
endocarditis. Again, blood cultures remained positive for a prolonged
period, and a long QT interval required the addition of a different,
newer antifungal agent, isavuconazole. Isavuconazole commenced because
it can shorten the QT-interval, unlike the older azole antifungals. A
repeat transthoracic echocardiogram was done, which showed a
bioprosthetic aortic valve with normal valvular motion, mild
periventricular thickening (likely postoperative changes), and a 5 x 8mm
non-mobile echogenic density attached to the right coronary cusp, likely
a calcification versus a healed vegetation. A repeated CT of the chest,
abdomen, and pelvis showed no pulmonary findings and similar abdominal
findings of splenomegaly and splenic infarct as the initial CT on
admission. A CT of the face showed no significant facial soft tissue
swelling or abscess—mild paranasal sinus mucosal disease involving the
maxillary sinuses and extensive dental disease. A gallium scan showed
marked splenomegaly, and activity was identified in the region of the
lower extremities, suggestive of marrow expansion, unchanged from
previous imaging. Blood cultures were repeated every forty-eight hours,
and with three consecutive negative blood cultures, she was discharged
in December 2022 to complete six weeks of therapy with isavuconazole and
to follow up with Cardiology and Infectious Diseases outpatient.
One month later, in January 2023, the patient followed up with her
primary care physician for complaints of dizziness, persistent nausea,
and vomiting. She had
repeated blood cultures that were positive for Candida
parapsilosis . Isavuconazole was discontinued because of
patient-reported side effects (persistent dizziness), and she was again
started on intravenous micafungin. A repeat transesophageal
echocardiography illustrated two 6mm mobile slender echocardiographic
densities attached to the ventricular surface of the aortic
bioprosthetic valve leaflets suggestive of endocarditis (Figure
3 ). Cardiothoracic surgery was consulted, and she had a redo aortic
valve replacement with a number 21 bovine Edwards bioprosthetic aortic
valve. Cultures of the aortic valve done at the operation were again
positive for Candida parapsilosis . Post-procedure, she received
six weeks of IV micafungin; her blood cultures remained negative for
fungal growth. Following completion of IV micafungin she was
transitioned to oral fluconazole 400 mg daily. She followed up with
infectious diseases in February and March 2023, where she remained
asymptomatic and clinically stable.