Clinical characteristics and prognosis of orbital invasive fungal … · 2019-06-28 · -iv-with...

Clinical characteristics and prognosis of orbital invasive fungal infection

Hye Sun Choi

Department of Medicine

The Graduate School, Yonsei University


Directed by Professor Sang Yeul Lee

The Master's Thesis submitted to the Department of Medicine,the Graduate School of Yonsei University

in partial fulfillment of the requirements for the degree of Master of Medical Science

Hye Sun Choi

June 2007

This certifies that the Master's Thesisof Hye Sun Choi is approved.

------------------------------------------------------ Thesis Supervisor : Sang Yeul Lee

------------------------------------------------------Bong Ki Lee : Thesis Committee Member#1

------------------------------------------------------Sung Joo Kim : Thesis Committee Member#2

The Graduate School Yonsei University

June 2007

ACKNOWLEDGEMENTS

본 논문을 완성하는 데는 참으로 많은 분들의 도움과 격려가 있었습니다 . 우선 지도교수를 받아들여 주시고 지속적인 관심과 사랑으로 제 연구를 이끌어주신 이상렬 선생님께 항상 감사드립니다 . 세심한 조언으로 제 연구의 잘못된점들을 자상하게 바로잡아주신 김성주 선생님께 감사드립니다 . 바쁘신 중에도 지도를 아끼지 않으신 이봉기 선생님께 감사드립니다 .

능력이 많지 않은 저를 늘 애정과 관심으로 지켜봐 주시는 김안과 선생님들의 따뜻한 성원에도 감사드립니다 .

저를 사랑으로 보살펴 주신 부모님과 시부모님께 감사드립니다 . 마지막으로 늘 저를 믿고 따라주며 변함없는 사랑을 보내준 소중한 남편과 사랑스런 자녀 정우 , 유진이와 함께 기쁨을 나누고 싶습니다 .

저자 씀

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<TABLE OF CONTENTS>

ABSTRACT ․․․․․․․․․․․․․․․․․․․․․․ 1

I. INTRODUCTION․․․․․․․․․․․․․․․․․․․ 3

II. PATIENTS AND METHODS․․․․․․․․․․․․․․ 6

1. STUDY PATIENTS․․․․․․․․․․․․․․․․․․ 6

2. STUDY DESIGN AND DATA COLLECTION․․․․․․․․ 6

3. ANTIFUNGAL THERAPY AND SURGICAL TREATMENT․․․ 6

4. DEFINITION․․․․․․․․․․․․․․․․․․․․․ 6

5. STATISTICAL ANALYSIS ․․․․․․․․․․․․․․․ 7

III. RESULTS․․․․․․․․․․․․․․․․․․․․․․ 8

1. DEMOGRAPHIC AND CLINICAL CHARACTERISTICS․․․․ 8

2. TREATMENT AND OUTCOMES․․․․․․․․․․․․ 11

3. RISK FACTORS FOR MORTALITY․․․․․․․․․․․ 12

IV. DISCUSSION․․․․․․․․․․․․․․․․․․․․ 13

V. CONCLUSION․․․․․․․․․․․․․․․․․․․ 18

REFERENCES․․․․․․․․․․․․․․․․․․․․․ 19

ABSTRACT (IN KOREAN)․․․․․․․․․․․․․․․․ 24

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LIST OF FIGURES

Figure 1. ․․․․․․․․․․․․․․․․․․․․․ 14

Figure 2. ․․․․․․․․․․․․․․․․․․․․․ 14

Figure 3. ․․․․․․․․․․․․․․․․․․․․․ 15

LIST OF TABLES

Table 1.․․․․․․․․․․․․․․․․․․․․․․ 9

Table 2.․․․․․․․․․․․․․․․․․․․․․․ 10

Table 3.․․․․․․․․․․․․․․․․․․․․․․ 11

Table 4.․․․․․․․․․․․․․․․․․․․․․․ 12

Table 5.․․․․․․․․․․․․․․․․․․․․․․ 12

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<ABSTRACT>


Hye Sun Choi

Department of MedicineThe Graduate School, Yonsei University

(Directed by Professor Sang Yeul Lee)

Background : Invasive fungal infection is a major cause of morbidity and

mortality in immuno-compromised patients. There have been many case reports on

clinical characteristics and prognosis of orbital invasive fungal infection. However,

few systematic studies on this disease have been reported. The objective of this

study was to evaluate clinical characteristics and prognosis of invasive orbital fungal

infection.

Patients and Methods : Medical records of Severance Hospital, Yonsei University

College of Medicine from 1995 to 2006 revealed 15 patients with invasive

orbital fungal infection. A retrospective cohort study was conducted to evaluate

the clinical characteristics, the radiological findings, the associated underlying

diseases, and the prognosis. Risk factors for mortality were analyzed.

Results : A total of 15 cases of orbital invasive fungal infections were included in this

study. Fourteen cases were of orbital invasive aspergillosis and one was of orbital

invasive mucormycosis. The mean age for all patients was 60 years. The most

common underlying disease was diabetes mellitus and paranasal sinuses were infected

in all cases. The most common ocular symptoms were periorbital swelling, orbital

pain and visual disturbance. The mortality rate associated with invasive fungal

infection was 40%. According to univariate analysis, variables significantly associated

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with invasive fungal infection-related mortality included use of steroids, fever, and

incorrect initial diagnosis.

Conclusions : Steroid use, fever and incorrect initial diagnosis were found to be

associated with high mortality rates of orbital invasive fungal infection. Further study

is necessary to determine optimal strategies for early diagnosis and appropriate

treatment.

��

Key words : invasive fungal infection, aspergillosis, mucormycosis, orbit

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Hye Sun Choi

Department of MedicineThe Graduate School, Yonsei University

(Directed by Professor Sang Yeul Lee)

I. INTRODUCTION

Invasive fungal infection is a major cause of morbidity and mortality in

immuno-compromised patients. The use of antibiotic, steroid,

immunosuppressive, and antineoplastic drugs, along with the increased longevity

of debilitated patients are predisposing factors.1 Other predisposing conditions

include diabetes mellitus, alcoholism, leukemia, human immunodeficiency virus

infection, prosthetic devices, liver cirrhosis, drug abuse, and advanced age.2-4

Invasive fungal infection involves lung, paranasal sinuses and skin, and

sometimes involves the orbit. The most common types of infection are

aspergillosis and mucormycosis.5

Aspergillosis is usually caused by Aspergillus fumigatus, Aspergillus flavus.5

Aspergillus is ubiquitous in our environment and is usually considered a

harmless saprophyte.6 It uncommonly causes infection in an immunocompetent

host.5-7 Aspergillosis is the most common cause of fungal sinusitis.8 The

inhalation of fungal spores into the nasopharynx and paranasal sinuses and an

altered host environment and response to the fungus are common factors in

these infections.5 Aspergillosis are classified as invasive or non-invasive

infections.7 The vast majority are non-invasive and have a good prognosis.

However, the invasive type behaves as a malignant neoplasm leading to bone

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destruction, intracranial extensions, and a high mortality rate.9.10 Pulmonary

infections are most common,11 but other organs can be infected, including the

brain, paranasal sinuses and orbit. Invasive orbital fungal infections usually start

in the paranasal sinuses initiating a fibrosing, granulomatous reaction. Secondary

orbital and intracranial extension is due to the slow, progressive, and often

painless nature of the disease.12-14 Aspergillosis can also cause orbital apex

syndrome, painful ophthalmolplegia and optic neuropathy.15-19

Mucormycosis is well known as an opportunistic fungal infection that rarely

arises in healthy individuals. It is usually caused by genera of the family

mucoraceae (Rhizopus, Mucor, and Absidia).5 Fungi form spores, which can be

inhalded into the human oral and nasal mucosa.19-20 In healthy individuals,

these spores are easily cleared by phagocytosis, but in the immunocompromised

host, germination and hyphae formation can occur.19 Hyphae formation allows

the organism to invade blood vessels.21 Mucormycosis can also involve

paranasal sinuses, orbit and brain. Some cases of rhino-orbital-cerebral

mucormycosis have been reported.1

This invasive fungal infection is difficult to eradicate using surgical

debridement combined with systemic and local antifungal agents, and there is a

high mortality rate due to intracranial extension.22 In some cases, orbital

exenteration is needed but efficacy is controversial.21

Intravenous amphotericin B has been the mainstay of medical therapy, but toxic side

effects, especially renal, in some patients require discontinuing the medications . New

systemic antifungal agents include liposomal amphotericin B preparations,

voriconazole, and caspofungin.23-25

Clinical presentations of orbital invasive fungal infection are similar to other

inflammatory orbital disease and neoplastic disease. Therefore, orbital invasive fungal

diseases can be misdiagnosed as another diseases such as idiopathic orbital

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inflammation and bacterial cellulitis with paranasal sinusitis.

There have been many case reports about clinical characteristics and prognosis of

orbital invasive aspergillosis. However, there are few reports on systematic studies of

this disease.

The objective of this study was to evaluate clinical characteristics, prognosis of

orbital invasive fungal infection and we investigated the risk factors for mortality

associated with orbital invasive fungal infection.

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II. PATIENTS AND METHODS

1. Study patients

From pathology, and medical records, 15 cases of invasive orbital fungal infection

were identified in patients registered between 1995 and 2006 at the Severance

Hospital, Yonsei University College of Medicine.

2. Study design and data collection

A retrospective cohort study was conducted to evaluate the underlying diseases,

clinical characteristics, radiological findings and prognosis of invasive orbital fungal

infection. Mortality was considered to be fungal infection-related when it occurred in

the active infection phase, and when there was no evidence of any other attributable

cause.

We retrospectively reviewed the patients' medical records and pathologic and

radiological findings. The data collected included: age; sex; underlying disease;

presenting symptoms and signs; laboratory findings; radiological findings;

involvement of other organs such as sinus or brain; antifungal therapy regimen; and

surgical treatment.

In-hospital mortality and visual outcomes were evaluated, and risk factors for

mortality were analyzed.

3. Antifungal therapy and surgical treatment

The choice of antifungal therapy regimens and surgical treatments were made by the

attending physician.

4. Definitions

The invasive fungal infection was defined using the standard definition as previously

described.26 Standard definition of invasive fungal infections classifies invasive

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fungal infection into "proven", "probable", and "possible" infections.26 In this study,

all cases are "proven" invasive fungal infections. "Proven" invasive fungal infection

was defined as a histopathologic examination showing hyphae from needle aspiration

or biopsy specimen with evidence of associated tissue damage (shown either

microscopically or unequivocally by imaging).

5. Statistical analysis

Fisher's exact tests, or χ2 tests were used to compare categorical variables when

necessary. Continuous variables were compared by independent t-test. To determine

independent risk factors for mortality, a logistic regression model was used. The

results of logistic regression analyses were reported as adjusted odds ratio(OR) with

95% confidence interval(CI). All p values were 2-tailed, and p<0.05 was considered

statistically significant. The SPSS for Windows software package version 11.0 was

used for this analysis.

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III. RESULTS

1. Demographic and clinical characteristics

A total of 15 patients with orbital invasive fungal infections were included in this

study. 14 patients had orbital invasive aspergillosis and 1 patient had orbital invasive

mucormycosis. Table 1 shows clinical summary of patients with orbital invasive

fungal infection. The mean age for all patients was 60 (range 39-83) years. Six

patients were male, and 9 were female. Demographic data and underlying diseases

are shown in Table 2. The most common underlying disease was diabetes mellitus

(86.7%, 13/15) and paranasal sinuses were infected in all cases (100%, 15/15). The

most common ocular symptoms were periorbital swelling (80%, 12/15), periorbital

pain (80%, 12/15) and visual disturbance (80%, 12/15). The rate of central nervous

system(CNS) involvement was 80% (12/15). There were 5 patients with a history of

using corticosteroids. Two of these were treated with steroids due to previous

medical conditions, and the others were treated with steroids due to incorrect initial

diagnosis.

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Table 1. Clinical summary of patients with orbital invasive fungal infection

* DM: Diabetes mellitus, C: controlled, U: uncontrolled, BMT: Bone marrow transplantation, ALL: Acute lymphocytic leukemia, LP: light perception

Sex/Age Diagnosis Underlying diseases Steroid use Involved area (Radiological findings) Initial diagnosis Visual outcome Outcome

M/83 Aspergillosis DM(U), Cardiomyopathy, Chronic renal failure

No Retrobulbar area and orbital apex.Maxillary and ethmoid sinus. Cavernous sinus.

Incorrect LP(-) Death

F/64 Aspergillosis DM(U), Aplastic anemia, Neutropenia, Steroid use, Immunosuppressant use

Yes Medial orbital wall and retrobulbar area. Ethmoid sinus. Cavernous sinus.


F/54 Aspergillosis DM(C) No Retrobulbar area and orbital apex. Maxillary, ethmoid, frontal and sphenoid sinus.Temporal lobe.

Correct LP(-) Death

F/45 Aspergillosis DM(U), End stage renal disease No Retrobulbar area.Maxillary, ethmoid, frontal and sphenoid sinus.

Correct LP(-) Survival

F/50 Aspergillosis DM(U) Yes Retrobulbar area and orbital apex. Ethmoid, frontal and sphenoid sinus. Temporal lobe.


F/65 Aspergillosis No Retrobulbar area. Maxillary sinus. Cavernous sinus. Correct LP(-) Survival

M/39 Mucormycosis DM(C) No Inferior orbital wall. Maxillary, ethmoid, frontal and sphenoid sinus. Infratemporal fossa.

Correct 20/30 Survival

M/71 Aspergillosis DM(U) No Retrobulbar area and orbital apex. Maxillary, ethmoid, and sphenoid sinus.


F/61 Aspergillosis DM(U),Ischemic heart disease

No Retrobulbar area and orbital apex.Maxillary, ethmoid, frontal and sphenoid sinus.Pterygopalatine fossa and dura.


F/54 Aspergillosis DM(U) No Superomedial quadrant of orbit. Maxillary sinus. Correct 20/40 Survival

M/60 Aspergillosis DM(U) No Retrobulbar area. Maxillary, ethmoid, frontal and sphenoid sinus. Dura.

Correct 20/100 Survival

F/73 Aspergillosis DM(U) Yes Retrobulbar area and orbital apex.Maxillary, ethmoid, frontal and sphenoid sinus.Temporal lobe.


F/71 Aspergillosis DM(U) Yes Inferior orbital fissure, and orbital apex.Ethmoid and sphenoid sinus.Pterygomaxillary fissure and foramen rotundum.

Incorrect 20/200 Survival

M/63 Aspergillosis DM(U) No Retrobulbar area, Maxillary and ethmoid sinus.Pterygopalatine fossa.


M/47 Aspergillosis ALL, BMT, Chemotherapy, Neutropenia, Steroid use, Immunosuppressant use

Yes Infraorbital foramen.Maxillary, ethmoid and sphenoid sinus. Dura.

Correct LP(-) Death

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Table 2. Demographic and clinical characteristics of patients with orbital

invasive fungal infection

Characteristics ValueAge, mean years±SD (range) 60.0±11.9 (39-83)Sex, No. of male/No. of female 6/9Diagnosis, No. of cases (%) Proven invasive aspergillosis 14 (93.3%) Proven invasive mucormycosis 1 (6.7%)Ocular symptoms, No. of cases (%) Periorbital swelling 12 (80%) Periorbital pain 12 (80%) Visual disturbance 12 (80%) Limitation of extraocular muscle 9 (60%)Duration of presenting symptoms, mean days±SD 39.7±36.5 (1-120)Duration from onset to diagnosis, mean days±SD 70.5±79.8 (7-320)Laboratory findings at admission White blood cell counts, mean cells/mm3(range) 8,087 (900-15,150) Hematocrit, mean % (range) 32.7 (20.0-41.9) BUN, mean mg/dL (range) 15.8 (6-46) Cr, mean mg/dL (range) 0.9 (0.5-2.1)Fever (Body temperature >38℃), No. of cases (%) Yes 6 (40%) No 9 (60%)Underlying disease, No. of cases (%) Diabetes mellitus 13 (86.7%) Organ transplantation 1 (6.7%) Steroid use 2 (13.3%) Neutropenia 2 (13.3%) Cardiovascular diseases 2 (13.3%) Immunosuppressant use 2 (13.3%) Hematologic malignancy 2 (13.3%) Renal disease 2 (13.3%)Involvement of central nervous system, No of cases(%) Yes 12 (80%)

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2. Treatment and outcomes

Among all patients, 14 (93.3%) patients had surgical treatment (Table 3). Radical

surgery means radical surgical debridement such as exenteration or total

sinusectomy. Restricted surgery means restricted surgical debridement such as partial

sinusectomy or mass excision. Permanent visual loss of affected eye occurred in 11

patients(73.3%) but 2 of these cases were also associated with diabetic retinopathy

and central retinal vein occlusion. The mortality rate associated with invasive orbital

fungal infection was 40% (6 of 15 patients, Table 4).

Table 3. Treatment of patients with orbital invasive fungal infection

Treatment

Surgery, No. of patients (%) 14 (93.3%) Radical surgery 4 (26.7%)

Restricted surgery 10 (66.7%)

Antifungal Agents, No. of patients (%) AmphotericinB 11 (73.3%) Liposomal amphotericinB 2 (13.3%) Itraconazole 1 (6.7%) Voriconazole 1 (6.7%)

No 3 (20%)Involvement of paranasal sinus, No of cases (%) 15 (100%) Maxillary sinus 12 (80%) Ethmoid sinus 13 (86.7%) Sphenoid sinus 9 (60%) Frontal sinus 7 (46.7%)Initial diagnosis, No of cases (%) Correct 10 (66.7%) Incorrect 5 (33.3%)

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Table 4. Outcomes for patients with orbital invasive fungal infection

3. Risk factors for mortality

According to univariate analysis, variables were significantly associated with

invasive fungal infection-related mortality included having use of steroids, fever, and

incorrect initial diagnosis(Table 5). Multivariate analysis did not reveal any

independent risk factors for mortality.

Table 5. Risk factors for mortality of patients with orbital invasive fungal

infection

* CNS : central nervous system

Variable No. of deaths/

No. of patients(%)

OR (95% CI) p

valueUse of steroid 16.0(1.093-234.248) 0.043

Yes 4/5 (80%) No 2/10 (20%) Presence of fever 40.0(2.014-794.270) 0.016

Yes 5/6 (83.3%) No 1/9 (11.1%) Initial diagnosis 0.063(0.004-0.915) 0.043

Correct 2/10 (20%) Incorrect 4/5 (80%)

Surgical treatment 0.392

Radical surgery 1/4 (25%) Restricted surgery 4/10 (40%) No surgery 1/1 (100%)CNS* invasion 0.229

Yes 6/12 (50%)

No 0/3 (0%)

Outcomes No. of deaths/no. of patients (%)

Visual loss 11/15 (73.3%)

Mortality 6/15 (40%)

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IV. DISCUSSION

Invasive orbital fungal infection is a rare but often fatal disease. In this study, most

cases were aspergillosis. Aspergillosis is the most common cause of the paranasal

sinus mycoses.8 Invasive aspergillosis can be either localized or fulminant. Localized

disease often starts in the sinuses and spreads to adjacent structures through focal bony

erosion or even through vessel walls. The fulminant form is characterized by multiple

organ involvement.27

Invasive aspergillosis is well documented in immunocompromised patients, with the

primary risk factors being neutrophil defects and corticosteroid use.27 Other

predisposing factors include HIV infection, diabetes mellitus, use of prosthetic devices

or trauma, excessive environmental exposure and possibly advanced age.27 In this

study, most patients had diabetes mellitus and other immunocompromised conditions.

However, invasive aspergillosis has been described in immunocompetent patients.7,28

Orbital extension of aspergillus sinusitis may often resemble a variety of

inflammatory or neoplastic conditions, and can transiently respond to corticosteroids. 29,30 This may lead to delayed diagnosis and subsequent progression of the infection.

In this study, 3 patients were initially diagnosed with inflammatory orbital disease, as

their first biopsies showed inflammatory reactions without fungal growth. These

patients were treated with high doses of corticosteroids for several weeks to months

and their prognosis was poor. It was difficult to confirm a diagnosis of aspergillosis by

histopathological examination of tissue samples obtained by endoscopic or other

procedures; in several patients, more than one biopsy was needed. High rates of

negative biopsy results have been reported especially since the fungus appears only in

late-stage clinical samples31-34( Fig.1). Therefore, if diagnosis is not made on first

biopsy and fungal infection suspected, a second biopsy should be performed,

especially before considering treatment with corticosteroids.

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A B

Fig.1. Periodic acid-Schiff stain shows dichotomous branching septate hyphae

consistent with Aspergillus species (A: X 100), (B: X 400)

CT scans or MRI of the sinuses, orbit and brain are important in diagnosing this

condition; as are determining the extent of disease, including bony erosion into

adjacent vital areas such as the orbit or skull base and planning the surgical approach.

Invasive aspergillosis may present with extension into the orbit or cranial cavity, and

may manifest radiologically as a paranasal mass contiguous with extension into the

orbital or cranial cavity. The presence of patchy hyperattenuation due to sulfates and

phosphates of magnesium, calcium and manganese within fungal debris is an indirect

indicator of fungal disease35(Fig.2).

A B C

Fig.2. (A) On initial diagnosis, axial computed tomography (CT) scan shows an

infiltrating mass occupying the right medial orbit extending through optic canal,

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superior and inferior orbital fissures, pterygopalatine fossa, and cavernous sinus with

bone destruction.(B) Five months after initial diagnosis, the mass increased and

extended to the ethmoid sinus. (C) Seven months after initial diagnosis, an axial CT

scan shows further increased extension of the lesion to infratemporal fossa with

petrous bone destruction.

MRIs show low signal intensity on T1-weighted images and central signal void,

with peripheral high signal on T2-weighted images, indicative of a central fungal mass

with surrounding waterlogged sinus mucosa. Also, postgadolinium T1-weighted

sequences show homogeneous bright enhancement of the lesion36(Fig.3).

Fig 3. Axial T1-weighted magnetic resonance imaging (MRI) with gadolinium

(Gd) contrast shows an enhancing lesion along right pterygomaxillary fissure and

orbital apex with right sphenoid sinus mass.

Diagnosis of invasive aspergillosis may be improved by assays for serum

Aspergillus antigen (galactomannan),37 a polysaccharide cell-wall component

released into circulation during fungal growth into thin tissues. Galactomannan

can be detected in the serum of patients with invasive aspergillosis during

fungal growth.40,41 This assay is noninvasive and despite some false results,

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useful in the early diagnosis of invasive aspergillosis.40,41

There is no uniformly accepted, completely effective treatment for orbital invasive

fungal infection. Management often begins with surgical debridement followed by a

systemic antifungal drug.

Some antifungals are used, such as polyenes (amphotericin), azoles (itraconazole

and voriconazole), and other newer classes such as lipid complex nystatin and

echinocandins. Among them, amphotericin B is a conventional drug for treatment

of invasive aspergillosis.24 Hargrove et al.21 reported that treatment with

amphotericin B correlated with improved survival. However, treatment is often

prolonged and can be complicated by adverse effects. The most serious

complication is renal dysfunction. Newer formulations, including lipid complex

and liposomal forms, have been developed to decrease the toxicity of

amphotericin B and indeed appear to be less toxic.25 There have been some

controlled trials to compare amphotericin and newer antifungal agents such as

voriconazole or echinocandins. In patients with invasive aspergillosis, initial

therapy with voriconazole led to better responses and improved survival and

resulted in fewer severe side effects than the standard approach of initial

therapy with amphotericin B.19 Data from various sources suggest that response

rates to the different drugs are only 40% to 60%.24 Of the azole class,

itraconazole and voriconazole are promising and are safer and easier to

administer than amphotericin B. Most experts recommend the maximum daily

dose of the chosen antifungal agents until the disease is controlled, and then

prolonged administration of oral itraconazole to ensure eradication.24

Radical surgical debridement of the orbit, adjacent sinuses, and skull base

area may be considered but is often complicated by other factors, including

difficulty in determining the extent of the lesion.

Sivak-Callcott et al.7 reported that factors associated with poor prognosis were

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delayed diagnosis, intracranial extension of infection, and histopathology

demonstrating hyphal invasion into blood vessel or adjacent tissue. Hargrove et al.21

described that age greater than 46 years, frontal sinus involvement, exenteration,

and fever greater than 101.5° F correlated with reduced survival. In this study,

risk factors such as having use of steroids, fever, and incorrect initial diagnosis were

found to be associated with high mortality rates of orbital invasive aspergillosis.

Surgical treatment was not statistically significant.

In this study, there were five patients with a history of using corticosteroids. Two of

these were treated with steroids due to previous medical conditions such as bone

marrow transplantation. However, in the other patients, attending physicians used

corticosteroid because their initial diagnosis was not correct. Correctness of initial

diagnosis is an important factor for proper treatment and good prognosis. For early

diagnosis of orbital invasive fungal infections, clinicians should suspect fungal

infections. Diagnostic approaches such as radiological evaluations, repeated culture

and biopsy are helpful for early diagnosis of fungal infections. There are new

diagnostic tests such as galactomannan or β-glucan.

In this study, the mortality of orbital fungal infection was 40%, and that of orbital

fungal infection with CNS invasion was 50%. There were 12 patients with CNS

invasion. Among those patients, only 3 patients had severe intracerebral invasion, and

they all died. However, in the other patients, fungal infections minimally invaded into

the CNS such as the dura or cavernous sinus, and the mortality of those patients was

33.3%.

Early detection and proper treatment may reduce the mortality associated with these

diseases.

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V. CONCLUSION

The orbital invasive fungal infection is an often fatal disease. Risk factors such as

use of steroids, fever, and incorrect initial diagnosis were found to be associated with

high mortality rates of orbital invasive fungal infection. Further study is necessary for

the determination of optimal strategies for early diagnosis and appropriate treatment.

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<ABSTRACT(IN KOREAN)>

안와 침습성 진균 감염증의 임상양상 및 예후

<지도교수 이상렬>

연세대학교 대학원 의학과

최혜선

배배배경경경 : 침습성 진균 감염증은 면역 기능이 저하된 환자에게서 주요 사망 원인중의 하나이다 . 안와의 침습성 진균 감염증의 임상적 특징이나 예후에 대한 많은 증례 보고는 있었으나 체계적인 연구는 거의 없었다 . 이번 연구는안와 침습성 진균 감염증의 임상적 특징 및 예후에 대해 분석해 보고자 하였다 .

대대대상상상 및및및 방방방법법법 : 1995년부터 2006년까지 연세대학교 세브란스병원에서 안와침습성 진균 감염증으로 진단받은 15명의 환자를 대상으로 의무기록 및 조직검사결과를 검토하여 기저질환 , 임상적 특징 , 방사선 소견 , 예후 등에 대한 후향적 코호트 연구를 수행하였다 . 사망과 관련된 임상적 인자들을 분석하였다 .

결결결과과과 : 14명의 안와 침습성 아스페르길루스증 (aspergillosis)환자와 1명의 털곰팡이증 (mucormycosis)환자 , 총 15명의 환자가 본 연구에 포함되었다 . 평균연령은 60세였으며 남자가 6명 , 여자가 9명이었다 . 가장 흔한 기저질환은 당뇨였으며 , 모든 홛자에서 부비동을 침범하였다 . 가장 흔한 안과적 증상은안와 부종 , 안와통 및 시력저하였다 . 침습성 진균감염과 연관된 사망률은40%(6/15)이었다 . 통계적으로 유의하게 사망률과 연관된 예후인자는 스테로이드의 사용 , 발열 , 잘못된 초기진단 등이었다 .

결결결론론론 : 안와 침습성 진균 감염증은 높은 사망률을 갖는 치명적인 질환이다 .

높은 사망률과 연관된 위험 인자로는 스테로이드의 사용 , 발열 , 잘못된 초기진단 등이 있는 것으로 나타났다 . 추후 연구를 통해 조기 진단과 적절한

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치료에 대한 최선의 지침이 필요할 것으로 생각된다 .

��

핵심되는 말 : 침습성 진균감염증 , 아스페르길루스증 , 털곰팡이증 , 안와

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