Keywords
mucormycosis - COVID-19 - fungal infections - urinary tract infections - diabetes
- steroid -
Rhizopus
Introduction
As COVID-19 continues to infect vast numbers of the population, an increasing number
of unusual and rare complications are being reported, some of them being fatal; one
such complication is secondary infections. Among the secondary infections of particular
importance are opportunistic fungal infections like mucormycosis that primarily affect
immunosuppressed or diabetic patients. Numerous cases of mucormycosis infections are
being reported particularly involving the lungs or paranasal sinuses; however, there
have been no reports of mucormycosis affecting the urinary tract in a patient with
a history of COVID-19 infection. We report a case of isolated fungal ball cystitis
without renal involvement or dissemination in a patient treated for COVID-19 pneumonitis.
Case History
A 60-year-old female patient presented with increased frequency of micturition and
dysuria. She had been tested positive for the severe acute respiratory syndrome coronavirus
2 reverse transcription polymerase chain reaction test, 8 weeks back with a computed
tomography (CT) severity score of 21 and was admitted to the intensive care unit for
the same. During the hospital stay, she was treated with high flow oxygen, prednisolone,
and broad-spectrum antibiotics.
She was recently diagnosed with type 2 diabetes mellitus during her admission and
was on monotherapy of metformin. After discharge, during follow-up she complained
of dysuria and lower abdominal discomfort. Her general examination was unremarkable
apart from suprapubic tenderness. Her biochemistry parameters were normal, blood sugar
levels were between 180 and 220 mg/dL, and glycosylated hemoglobin was 5.8%. Urinalysis
revealed few epithelial cells, increased red blood cells—138/high-power field (HPF)
and raised leukocytes—146/HPF. Glucose levels in urine were 32mg/dL. She was treated
with oral antibiotics for 10 days, her symptoms persisted and she was restarted on
second-line antibiotics and a urine sample was sent for culture, the culture was negative
for bacterial growth. On ultrasonography (USG), right-sided hydronephrosis and hydroureter
were detected. On further evaluation with CT study, there was circumferential enhancing
thickening seen involving the right lower ureter with mild hydronephrosis and hydroureter
in entire extent and evidence of a filling defect in the urinary bladder close to
the vesicoureteric junction seen on excretory phase images ([Fig. 1]). CT scan of the thorax revealed sequelae of viral pneumonitis. The possibility
of urothelial carcinoma was considered on radiological imaging. Cystoscopy was performed
that revealed a whitish friable mass-like lesion, which looked like a tuft of cotton
in the urinary bladder close to the right ureteric orifice ([Fig. 2]). The adjacent bladder mucosa appeared erythematous. The mass-like lesion was resected
histology that revealed abundant fungal hyphae, which were broad, nonseptate with
irregular branching at right angles ([Fig. 3]). There was no evidence of atypical cells seen. The sample was sent for bacterial
and fungal culture. The culture showed rapid growth on potato dextrose agar within
72 hours in the form of whitish layers. Lactophenol cotton blue mount of the growth
revealed rhizoids, sporangium, and sporangiophore appearance characteristic for Rhizopus species ([Fig. 3]). Thus, the diagnosis of vesical mucormycosis was reached.
Fig. 1 The right kidney shows a suboptimal nephogram with hydronephrosis (white arrow).
The right lower ureter appears dilated with enhancing urothelial thickening (red arrow).
A filling defect (yellow arrow) is seen in the urinary bladder close to the vesicoureteric
junction on excretory phase images.
Fig. 2 Cystoscopy image revealing a whitish friable mass-like lesion looking like a tuft
of cotton in the urinary bladder close to the right ureteric orifice(arrow) and erythematous
changes seen in the adjacent bladder mucosa (arrowhead).
Fig. 3 Tissue sections (hematoxylin and eosin × 400) reveal nonseptate hyphae of mucormycetes
with wide-angle branching (right) and lactophenol cotton blue mount revealing rhizoids,
sporangium, and sporangiophore appearance characteristic for Rhizopus species (left).
The patient was started on intravenous liposomal amphotericin B that was continued
for 6 weeks followed by posaconazole 300 mg daily for 4 weeks. Her blood sugars were
controlled on metformin and sitagliptin. She was asymptomatic after 10 weeks of antifungal
treatment. Urinalysis was unremarkable with no growth seen on culture. Repeat USG
and cystoscopy revealed response to treatment.
Discussion
In the current COVID-19 pandemic, there has been a rise in the incidence of mucormycosis
in India, due to multiple factors such as the high prevalence of Mucorales in the
environment, steroid overuse in the management of COVID-19 resulting in new-onset
diabetes, and irrational use of broad-spectrum antibiotics. Mucormycosis is caused
by fungi of the order Mucorales that belongs to a class of Zygomycetes. Isolated mucormycosis
involving the urinary bladder is rare.[1]
Very few cases of mucormycosis involving the urinary bladder have been described in
the literature. A vesical noninvasive Rhizopus fungal ball infection with ascending pyelonephritis has been described previously
in a patient with poorly controlled diabetes mellitus.[2] However, isolated bladder mucormycosis has been reported previously in an elderly
patient with a permanent bladder catheter.[3] Fungal bezoars causing ureteric obstruction
are rare. Candida is the most common causative organism, with other fungi being aspergillus, penicillium,
and mucor.[3]
These patients may present with nonspecific symptoms or symptoms of urinary tract
infections as in our patient. Often nasal cavity, paranasal sinuses, or the lungs
are the primary focus of infection with involvement of other organs by dissemination
from these sites. However, in our case, there was no evidence of involvement of other
organs on clinical as well as imaging evaluation.
USG findings are usually nonspecific. It can enable the identification of hydronephrosis
and hydroureter in cases of a fungal bezoars causing ureteric obstruction. If large
enough, fungal balls may be identified as hypoechoic round masses with no internal
vascularity in color doppler study. In our case, USG failed to identify the fungal
ball. CT findings include bladder or ureteric wall thickening, hydronephrosis, and
hydroureter. Like in our case, vesical fungal bezoars have been described as radiolucent
masses that appear as filling defects on excretory or retrograde urography study.[4] Cystoscopy may reveal ulcerated bladder mucosa, multiple mounds of tissue, and architectural
distortion of the bladder.[5]
[6] The presence of broad septate or pauciseptate hyphae with wide-angle branching is
characteristic of Mucorales fungi.[2]
The presence of suspicious features on imaging and identification of Mucorales on
fungal culture calls for prompt intervention. Commonly a combination of medical as
well as surgical management is necessary. The management of predisposing factors such
as control of blood sugar levels or reduction in immunosuppressive therapy is also
of utmost importance.
Early diagnosis is crucial in the management of mucormycosis as prompt treatment can
prevent dissemination of disease process and involvement of critical organs, thus
allowing a favorable prognosis.