Journal of Medical Microbiology (2013), 62, 652–654 DOI 10.1099/jmm.0.

044222-0

Case Report Highly effective unconventional management

of aspergillosis of the left maxillary sinus in an
11-year-old girl with rhabdomyosarcoma
embryonale of the frontal sinus
Jaroslaw Peregud-Pogorzelski, Pawel Wawrykow, Sebastian Wozniak,
Anna Zakowska and Andrzej Brodkiewicz
Correspondence Department of Pediatrics, Pediatric Hematology and Oncology, Pomeranian Medical University,
Jaroslaw Peregud-Pogorzelski Szczecin, Poland
jperegud@mp.pl

Received 19 June 2012
Accepted 12 December 2012
Invasive fungal infections are common causes of death in children treated for malignancies, and
therefore present an important and growing clinical problem. Fungal invasion usually affects
immunocompromised patients, but increased incidences are also associated with intensification
of antineoplastic therapy and increased numbers of organ and bone marrow transplantations.
Fungal infections in parameningeal and cerebral locations carry high risks of treatment failure. We
describe the case of an 11-year-old female patient with rhabdomyosarcoma embryonale of the
frontal sinuses with metastases to the neck lymph nodes, treated according to the CWS 2002
protocol for high-risk patients. Left maxillary sinus aspergillosis was diagnosed during
chemotherapy following radiotherapy, and 56 days after surgical excision of the tumour. No effect
was achieved by use of amphotericin B. Further treatment included intravenous voriconazole at
6 mg per kg body weight every 12 h for 2 weeks, followed by oral voriconazole at 4 mg per kg
body weight twice daily for 6 months. Simultaneous excision of necrotic tissues from the nasal
cavity, ethmoid bone, maxillary sinus and frontal recess was performed. The sinus was kept open
for 3 weeks to allow voriconazole lavage every 12 h for 3 weeks. This unconventional treatment
resulted in eradication of sinus aspergillosis and allowed intensive chemotherapy to be continued
with no recurrence of aspergillosis.

Introduction sinus and left maxillary sinus. Unconventional manage-

Primary and secondary immunodeficiencies, use of immu- ment consisted of maxillary sinus surgery with excision of a
nosuppressive drugs or broad-spectrum antibiotics, long- necrotic mass with septate hyphae, and local and systemic
term parenteral nutrition, and in-dwelling central catheters amphotericin and voriconazole treatment. This therapeutic
all predispose to invasive fungal infections (Hasan & regimen resulted in successful eradication of the infection
Abuhammour, 2006; Abbasi et al., 1999; Cuccia et al., and allowed continuation of chemotherapy with no infec-
2000; Müller et al., 2002). Prolonged neutropenia during tion recurrence.
antineoplastic therapy, impaired granulocyte function dur-
ing the course of malignancy, abnormal T-cell immunity in
patients after bone marrow transplantation, and procedures Case report
performed for the treatment of solid tumours are also risk An 11-year-old female patient with rhabdomyosarcoma
factors for fungal infections (Hasan & Abuhammour, 2006; embryonale located in the frontal and left maxillary sinuses
Müller et al., 2002; Cesaro et al., 2003). Most of these and with metastatic disease in the neck lymph nodes was
risk factors are present in children with malignancies. The treated according to the Cooperative Weichteilsarkom Studie
central nervous system is most frequently involved in blood- (CWS) 2002 protocol (ftp://ftp.uke.uni-hamburg.de/pub/
borne infections, while respiratory tract involvement results temp/CWS-2002P-Oktober03_Korrektur.pdf) for high-risk
from airborne infections (Hasan & Abuhammour, 2006; patients. Adjuvant chemotherapy for 7 weeks was followed
Cuccia et al., 2000; Müller et al., 2002). Invasive fungal by total excision of the tumour within the macroscopic
sinusitis remains an important diagnostic and therapeutic
margins of intact tissue. Simultaneous postoperative chemo-
problem associated with high mortality.
therapy and radiotherapy were introduced. After completion
We present a case of invasive fungal sinusitis in a child of radiotherapy and 56 days after sinus surgery, the patient
treated for rhabdomyosarcoma embryonale in the frontal developed fever and mucus and pus discharge from the left
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nasal duct, with concomitant left eyelid oedema. Cultures
from the nasal duct discharge revealed the presence of
filamentous fungi. Magnetic resonance imaging showed the
presence of a pathological mass in the left maxillary sinus
but no signs of bone destruction adjacent to the brain (Fig.
1). No fungal pulmonary involvement was found. The
patient underwent excision of necrotic tissues from the
frontal sinus orifice and her left maxillary sinus was opened.
The fever, left eyelid oedema and left nasal discharge
resolved after 5 weeks of treatment with amphotericin B at
1 mg per kg body weight. Amphotericin B soluble in sodium
deoxycholate was used. However, following the next
chemotherapy cycle (16th week of treatment according to
the CWS 2002 protocol), her fever recurred, together with
left orbit oedema and left eye subconjunctival haemorrhage.
Magnetic resonance imaging again revealed pathological
changes within the left maxillary sinus. Systemic and local
amphotericin B proved ineffective. Cultures from the
discharge from the left nasal cavity revealed Aspergillus niger.
Because of the overall severe status of the patient, a wide
antrostomy of the left maxillary sinus with excision of the
fungal mass was performed, and the nasal cavity, ethmoid
bone and frontal recess were cleaned. Histopathological
studies of masses removed from the sinus revealed the
presence of hyphae resembling Aspergillus sp. The galacto-
mannan and Candida mannan antigens proved to be
negative.
Subsequent treatment consisted of intravenous voricona-
zole at 6 mg per kg body weight every 12 h for 2 weeks,
followed by oral voriconazole 4 mg per kg body weight for
6 months. Additional sinus lavage with voriconazole was
performed twice daily for the first 3 weeks. Due to lack of
technical support no monitoring of therapeutic levels in
blood and cerebrospinal fluid was performed. The patient’s
Fig. 1. Pathological mass filling the left maxillary sinus.
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Antifungal management in sinus aspergillosis
general status improved and her left eye oedema resolved.
Control imaging studies (Fig. 2) and left maxillary sinus
endoscopy revealed total regression of the fungal changes.
No recurrence of fungal infection was observed, despite
continuation of intensive chemotherapy.
Discussion
Sinus invasion is one of the most frequent manifestations
of fungal infection in patients treated for malignancies.
Invasive fungal sinusitis is caused by invasion of pathogens
through the nasal mucous membrane, followed by
dispersion of fungal spores to the ethmoid bone, orbit or
palate (Hasan & Abuhammour, 2006; Müller et al., 2002).
The central nervous system may be affected in some cases.
Airborne infection leads to pulmonary invasion in 70 % of
cases, while sinus involvement is seen in 18 % (Abbasi et al.,
1999). Invasion by Aspergillus species is associated with
poor prognosis, and the mortality in these patients ranges
from 50 % to almost 100 % with central nervous system
invasion (Leroy et al., 2006).
The long-term and oligosymptomatic course of the disease,
and the lack of sufficiently sensitive diagnostic methods,
mean that fungal infections may remain undiagnosed for a
prolonged period. Additional obstacles result from the
presence of non-specific signs, including fever, headache,
cough, pus discharge from the nasal cavity and pharyngeal
pain. Fungal infection within the sinuses often coexists
with pulmonary involvement (Hasan & Abuhammour,
2006; Gupta et al., 2006). Less common, but still
characteristic features of fungal sinusitis include blocked
nose, bleeding or pus discharge from the nares, deforma-
tion of facial soft tissues, orbital oedema, endophthalmus,
visual impairment and destruction of bones. The maxillary,
Fig. 2. Residual thickening of the left maxillary sinus mucosa after
completion of therapy.
653
J. Peregud-Pogorzelski and others
ethmoid and frontal sinuses are most commonly involved
in patients younger than 15 years (Abbasi et al., 1999;
Gupta et al., 2006).
Of approximately 1000 species of Aspergillus, fewer than 20
are pathogenic in humans. Severe infections of the
respiratory tract and sinusitis in children suffering from
malignancies are caused by Aspergillus fumigatus and
Aspergillus flavus with equal frequencies (Hasan &
Abuhammour, 2006; Müller et al., 2002). In contrast,
central nervous system invasion with A. niger is rare, and
according to Dotis et al. (2007), the cerebral infection rate
in paediatric populations is only 1.8 %.
Treatment of invasive fungal infections is difficult because
of the relatively small choice of antifungal agents and their
limited penetration to the affected tissues, especially in the
case of parameningeal or cerebral infections (Abbasi et al.,
1999). In the present patient, Aspergillus was isolated from
the nasal ducts and therapy was initiated with amphoter-
icin B, with transient improvement and resolution of fever,
left eyelid oedema and left nasal discharge. However, the
subsequent chemotherapy cycle was followed by recurrence
of the fungal infection, and treatment with systemic and
local amphotericin B proved ineffective. A. niger was
identified by microbiological techniques, and magnetic
resonance imaging revealed a pathological mass within the
frontal, maxillary and ethmoid sinuses. Because of her
severe general status, the patient was scheduled for surgical
excision of the necrotic masses from the nasal cavity,
ethmoid bone, maxillary sinus and frontal recess.
Simultaneous antifungal treatment was established with
voriconazole, a broad-spectrum antifungal agent covering
Candida and Aspergillus aetiologies, representing the species
most frequently seen in patients with malignancies. This
patient initially received 2 weeks of treatment with intra-
venous voriconazole twice daily at a dose of 6 mg per kg
body weight, followed by oral voriconazole at a dose of 4 mg
per kg body weight twice daily for 6 months. Nasal cavity
and maxillary sinus lavage was also performed twice daily
with voriconazole solution at a dose of 100 mg for the first
3 weeks. Definitive data on the recommended duration of
antifungal treatment in similar cases are currently lacking
(Abbasi et al., 1999; Kalwak, 2009).
It should be noted that the relatively low sensitivity and
specificity of microbiological and serological methods for
detecting localized fungal infections means that imaging
studies play an important role in the diagnostic process.
According to previous reports, imaging findings suggestive
of fungal infections are present in approximately 50 % of
cases. Surgical treatment is applied, not only for invasive
fungal sinusitis, but also for pulmonary, articular and central
nervous system manifestations of the disease (Hasan &
Abuhammour, 2006; Gupta et al., 2003; Sasindran et al.,
2008; Thomas et al., 2003). Despite the use of modern
surgical techniques, surgery in these patients carries a high
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(50 %) risk of failure. However, surgery may represent the
only option for total evacuation of the affected tissues and
for acquiring sufficient diagnostic material to confirm the
fungal aetiology of the infection (Hasan & Abuhammour,
2006; Leroy et al., 2006).
Concluding remarks
Parameningeal aspergillosis in patients with malignancies
treated with chemotherapy still has a poor prognosis, and
all available therapeutic options should be considered for
the treatment of these infections. Unconventional therapy
in the present case included the use of systemic antifungal
agents and surgical excision of necrotic tissues from the
nasal cavity, ethmoid bone, maxillary sinus and frontal
recess. The sinus was kept open for 3 weeks to enable
repeated voriconazole lavage. This treatment strategy
resulted in the eradication of sinus aspergillosis, whilst
allowing continuation of intensive chemotherapy, with no
recurrence of aspergillosis.
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Journal of Medical Microbiology 62