FUO as first presentation of candida vertebral osteomyelitis;
case report Key Clinical MessageCandida osteomyelitis is a rare disease. The optimal management of
candida osteomyelitis is not clearly defined but most recommendations
advise prolonged antifungal therapy in addition to surgery. that can
lead to the complete resolution of symptoms.Abstract Candida osteomyelitis is a rare disorder however its incidence has
drastically risen especially during the last three decades. Diagnosis is
usually delayed due to nonspecific symptoms. Thus its management is
not done at the proper time which leads to increased morbidity. The
optimal management of candida osteomyelitis is not clearly defined but
most recommendations advise prolonged antifungal therapy in addition to
surgery. Here we report an immunocompetent case of candida osteomyelitis
that presented with prolonged FUO as her first presentation.
Fortunately, her symptoms completely resolved after prolonged medical
therapy despite the delay in diagnosis due to her unusual presentation.
Keywords: vertebral osteomyelitis, candida osteomyelitis
Introduction
Candidemia, previously considered transient and harmless in most cases,
is now known to be frequently complicated by deep-seated infections in
various parts of the body like Eye, kidney, liver, skin, cardiac, and
etc. Bone and joint infections are rare secondary
foci.1
Fungal spondylodiscitis is rare and consists of 5% of all cases of
spondylodiscitis, candida species are the most frequent agent.
Fungal Monilia psilosis osteomyelitis was first described by
Conner in 1928. Keating reported four other patients
with Monilia osteomyelitis involving long bone sites in 1932. The
first report of Candida osteomyelitis came back in
1970.2.3
The incidence of invasive candida infection has risen dramatically in
the last 30 years due to an increased number of immunocompromised
patients, invasive procedures, and the use of broad-spectrum
antibiotics although it is still extremely rare.4
The unusual presentation of candida vertebral osteomyelitis (CVO) makes
early recognition of the disease difficult therefore depriving the
patient of timely intervention and can cause significant morbidity. The
treatment strategies of invasive candida infections have evolved, it
consists of medical antifungal therapy for a long time and in most
cases, surgery is a part of the main treatment. The Infectious Diseases
Society of America (IDSA) recommendations for CVO include surgical
debridement and an initial course of amphotericin B for 2–3 weeks,
followed by fluconazole for a total duration of 6–12 months
.1. 3.5 Here we report a patient without significant
past medical history who was diagnosed with CVO several months after
pancreatic surgery. She received prolonged antifungal treatment and her
symptom was completely resolved without surgery.
Case presentation
A 70-year-old woman with incidental findings of distal pancreatic mass
during screening workup came to our clinic for further evaluation. EUS
and FNA were performed. The pathology specimen was reported
as adenocarcinoma. Distal pancreatectomy, splenectomy, adrenalectomy was
performed due to vascular involvement. Port was placed in the right
internal jugular vein at the time of surgery because of a lack of proper
peripheral vascular access. Her early postoperative period was
uneventful. On the fifth postoperative day, she became febrile.
Abdominal ultrasonography showed peripancreatic collection. A pigtail
catheter was inserted under US guidance, the collection was drained and
sent for a culture that turned out to be negative. Antibiotics were
continued, she had a persistent low-grade fever.
On the 21st postoperative day, she had high-grade
drenching fever with respiratory distress, chest CT angiography showed
partial thrombosis of the distal part of SVC containing air bubbles,
suspicious for the infected clot. The port was brought out and sent for
a culture that turned out positive twice for candida, simultaneous blood
culture was negative three times. The abdominal CT scan was normal at
that time. Laboratory testing gives generally nonspecific results. Full
sepsis workup investigation turns out to be non-diagnostic. Physical
exams including the neurologic exam revealed no abnormality.
Antifungal therapy (caspofungin) was added to her regime although the
positive candida culture of the port was regarded insignificant by our
infectious disease specialist. She was discharged with caspofungin in
good physical condition after 30 days, she was not febrile anymore. Two
weeks after discharge she suffered from severe weakness and back pain.
The patient was readmitted to the hospital and conservative
management was done. The abdominal CT scan seems to be normal. After
Three months another thoracoabdominal CT scan was performed due to
persistent weakness and back pain that showed destruction of two
thoracic vertebral bodies (T6,7) Figure1, the neurologic exam was
normal, she had no difficulty with ambulation apart from her severe
physical weakness. Thoracic MRI has been performed that revealed
destruction of T6, T7. Figure2. Biopsy was taken from the affected
vertebral body, candida was cultured and diagnosis of CVO was made.
Fluconazole was initiated with a dose of 400mg daily, her persistent
fever was subsiding gradually, she continued antifungal therapy for one
year, now she has normal neurologic exam, with no back pain, however she
complained of occasional pain on the left side of lumbar vertebrae.
Discussion
Invasive fungal infections including nosocomial bloodstream infections
due to Candida species have increased significantly over the last
years.3 Despite the increase in the frequency of
fungemia, infection by Candida. spp is also a rare cause of spinal
infection. 10CVO typically occurred
in immunocompromised patients or in intravenous drug users previously.
Increased antibiotic use, placement of a central venous catheter,
steroid use or other immunosuppression, surgery, placement of a urinary
catheter, underlying malignancy, diabetes, alcohol abuse, parenteral
nutrition, hemodialysis, burns, neutropenia, and the isolation
of Candida organisms from >2 body sites are reported
in the literature as risk factors for candidemia. These risk factors can
alter the patients’ natural flora, outreach the risk for candidemia from
an intravascular device, or cause some level of immunosuppression.
In 1998, Anderamahr reported a case of lumbar spondylitis due
to Candida and then after reviewing 31 adult cases with vertebral
osteomyelitis from the literature. In our review of the published
English literature through PubMed for candida spondylodiscitis, about
200 cases of candida spondylodiscitis were found mostly reported in the
last two decades and most of them were in immunocompromised patients or
IV drug users. 2.8CVO may occur either simultaneously or several months after an episode
of verified or suspected candidemia. In patients with suspected
candidemia which is not verified by culture, risk factors for candidemia
can be noticed in two-thirds of them. 4CVO can enlace
any bone however the axial skeleton is most involved in adults.
According to some studies, an antifungal regimen enough to clear the
episode of fungemia may not prevent the occurrence of this late
complication.6 Blood culture results are reported to
be positive in only 50% of cases of documented disseminated
candidiasis 11.12 Therefore, cases with prior
candidemia may not be detected only through blood culture
.4Because CVO is considered as a complication of an
episode of candidemia, a high index of suspicion must be retained for
patients with a history of candidemia who present with back
pain.9Early diagnosis of CVO is difficult. The lapse in diagnosis between the
onsets of symptoms to the recognition of CVO has been reported as
ranging from 1 month to several years 16.17 With an
average of 3.3 months.2 This can be due to delay in
presentation, investigation, vogue symptoms, the insidious course of the
disease, the lack of a specific diagnostic test, and the reluctance of
clinicians to see Candida spp. as a true
pathogen.6.7
The most common presentation of the disease is back pain mostly in the
lower thoracic to the lumbosacral spine. Only one-third of patients had
a fever at the presentation. In our research, we don’t find a case of
CVO who presents with prolonged FUO as the first presentation like our
case. About 20% of patients had neurological
deficits.7. 13
Results of laboratory tests except microbiological tests were
nonspecific; they frequently consisted of an elevated ESR but a normal
WBC count. Therefore, clinical and standard laboratory findings
are incomplete to precisely diagnose CVO. A high clinical index of
suspicion, with proper radiographic studies followed by verifying with
microbiological tests, helps to diagnose the disease appropriately.
Erosive and destructive vertebral changes may be seen in plain
radiography, but with weeks to months’ delay .14 There
is no characteristic CT finding for CVO, however, CT scanning can show
earlier bony changes and can appraise the presence of paravertebral or
spinal canal extension, too. 15 The culture of
a biopsy specimen is required for the definitive microbiological
diagnosis of CVO. Multiple needle biopsy specimens should be taken from
involved vertebral bodies, intervening disks, and paravertebral
soft tissues, to make a definite diagnosis. If the results for primary
needle biopsy specimens are negative, the procedure should be repeated.
If a second set still reports negatively, then performing an open
biopsy should be considered seriously, because empirical therapies for
bacterial, mycobacterial, or fungal osteomyelitis are vastly different
and associated with toxicities that require close
monitoring.4.7Patients with CVO have a good prognosis and most of them without
significant comorbidities were clinically completely cured, similar to
patients with bacterial vertebral osteomyelitis .13The
cure rate for cases with CVO is reported to be about 85%. But without
treatment, the disease progresses and leads to vertebral destruction and
spinal cord and neural compression. As soon as osteomyelitis is dubious,
investigations with proper imaging and percutaneous biopsy should be
done followed by medical therapy in order to halt the advancement of
bony destruction and therefore barricade the need for surgery. Surgical
debridement, fusion, and stabilization combined with medical therapy can
successfully extricate the infection and resolve the neurological
deficits if vertebral collapse and spinal cord compression happen. In
our case, despite the destruction of lumbar bodies, the patient
was fully recovered without any surgery with prolonged antifungal
therapy. Little is known about the optimized management of candida
spondylodiscitis, yet fluconazole seems to be effective in most
cases and prolonged treatment of several months seems to be vital as in
our case .1
In the immunocompetent case that we present without past medical
history, it seems that prolonged antibiotic use, plus central venous
catheterization susceptible our patient to candidemia. It manifests with
prolonged FUO, and after months low back pain added to her symptoms that
finally led to definite diagnosis and proper management.
We hope that Case reports such as this one help to increase the
experience in the management of this rare disease.