Scandinavian Journal of Infectious Diseases, 2014; 46: 325–330
CASE REPORT
Aspergillus mastoiditis in an immunocompetent patient: A case report and review of the literature
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MONA YOUSSEF1, MARC BASSIM2, NINA SHABB3 & SOUHA S. KANJ1 From the 1Department of Internal Medicine, Division of Infectious Diseases, 2Department of Otolaryngology, and 3Department of Pathology and Laboratory Medicine, American University of Beirut Medical Center, Beirut, Lebanon
Abstract Aspergillus mastoiditis usually occurs in immunocompromised patients. There are a few isolated reports in the literature involving immunocompetent patients. We hereby describe the case of an immunocompetent patient diagnosed with invasive Aspergillus mastoiditis, which was treated successfully, and review the literature pertaining to this condition. The common clinical presentations, putative pathophysiology, and recommended therapy are discussed.
Keywords: Aspergillus, mastoiditis, immunocompetent, otitis
Introduction Aspergillus species can be identified by gross and microscopic appearance as a mold with septate hyphae of 2 to 4 µm in diameter. Human exposure is common, however, human infection is infrequent in immunocompetent patients. Aspergillus mastoiditis is usually reported in cancer patients. We present a case report of Aspergillus mastoiditis in immunocompetent patient who was treated for 6 months before the diagnosis was made by surgery. Case report A 67-y-old man presented with a 6-month history of severe left-sided hearing loss, left tinnitus, and chronic otorrhea from both ears. This was associated with dizziness that had increased in severity over the preceding month, and a chronic headache. He denied fever, chills, or weight loss. He had no respiratory, gastrointestinal, urinary, or dermatologic complaints, and had received topical and systemic antibiotics without improvement. His medical history was otherwise unrevealing. Physical examination revealed whitish debris in both ears and a left facial paralysis. The rest of his
exam was otherwise unremarkable. An audiogram confirmed profound hearing loss in both ears with very poor discrimination. Computed tomography (CT) imaging of the temporal lobes with multiplanar reconstruction showed diffuse opacification of both mastoid air cells, with erosion of the posterior surface of the petrous part of the temporal bone including the posterior half of the inner ear. The erosion pattern included areas of severe bone lysis with segments of diffuse sclerosis (Figure 1A). Magnetic resonance imaging (MRI) showed an erosive and lytic lesion involving the posterior wall of the left petrous pyramid with significant widening of the vestibular aqueduct, erosion of the posterior wall of the superior semicircular canal, and extension into the mastoid air cells with complete opacification of the mastoid air cells, which in view of preserved bony septae suggested retained secretions. An endolymphatic sac tumor was highly suspected. Other diagnoses such as metastatic bone disease and paraganglioma were also considered. A positron emission tomography (PET) scan, ordered to rule out a metastatic origin of this lesion, was negative.
Correspondence: Souha S. Kanj, Division of Infectious Diseases, Department of Internal Medicine, American University of Beirut Medical Center, PO Box 110236, Beirut, Lebanon. Tel: ⫹ 961 3 835845. Fax: ⫹ 961 1 370814. E-mail: [email protected] (Received 22 October 2013 ; accepted 25 October 2013) ISSN 0036-5548 print/ISSN 1651-1980 online © 2014 Informa Healthcare DOI: 10.3109/00365548.2013.867073
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Figure 1. (A) An axial cut from the CT scan of the temporal bone revealing erosion of the posterior wall of the temporal bone and into the labyrinth, with partial erosion of the superior semicircular canal, along with complete opacification of the mastoid. (B) Gomori’s methenamine stain of the surgical specimen: numerous acute angle branching septate hyphae are seen.
Based on the above findings, surgical excision of this mass through a translabyrinthine approach was done. Intraoperative findings revealed a very vascular lesion filling and eroding the mastoid air cells and extending into, and occasionally through, the dura of the posterior fossa and jugular bulb. The lesion was completely excised with no gross residual disease. Intraoperative frozen section specimens were not conclusive. The final pathology result showed severe inflammatory changes with necrosis, bone destruction, and fibrosis, and no evidence of tumor. Numerous acute angle branching septate hyphae were seen, raising the diagnosis of Aspergillus mastoiditis (Figure 1B). A serum sample for Aspergillus galactomannan was also positive, confirming the diagnosis of Aspergillus mastoiditis. Based on the above, the patient was started on itraconazole 200 mg per os twice a day for a total of 3 months. At the 2-month follow-up visit, the patient had markedly improved regarding all his symptoms. Discussion Fungal mastoiditis is an uncommon but serious condition that usually occurs in immunocompromised patients, such as those with leukemia, acquired immunodeficiency syndrome, or diabetes mellitus. The first such case was reported by Petrak et al. in 1985 in an immunocompromised host [1]. The most commonly reported organisms were Mucor and Aspergillus species. A limited number of cases have been reported in immunocompetent adults. In 2009, van Tol and van Rijswijk reported the case of an immunocompetent patient who underwent mastoidectomy because of unexplained, progressive otalgia. Histopathology and cultures yielded Aspergillus fumigatus [2]. Their report also included a review of 6 cases previously
described in the literature [3–8]. All were diagnosed with Aspergillus mastoiditis with no predisposing risk factors. More recently, in 2012, Varghese et al. reported the largest case series of fungal otomastoiditis in immunocompetent adults [9]. Aspergillus infection in the temporal bone can have 1 of 3 different presentations. The most benign form is a non-invasive, localized infection that responds to conservative surgical removal. The second form is an invasive osteolytic presentation, with diffuse granulation tissue and fibrosis, similar to the case described in this report. This is the presentation most commonly reported in immunocompetent patients. The third type, typically presenting in immunocompromised patients, is a fulminant angioinvasive infection with no granulomatous response and very rapid deterioration [10,11]. Four routes of entry of fungal infection to the middle ear are typically discussed: tympanogenic, meningogenic, hematogenic, and nasopharyngeal [1,12]. The patients present frequently with symptoms of intermittent otorrhea, intractable ear pain, chronic dizziness, and progressive cranial nerve palsy. Interestingly, evidence of facial nerve involvement was noted in almost all of the patients [2]. Almost all cases were diagnosed as chronic otitis and mastoiditis with bacterial infections and were treated as such, mainly with topical and systemic antibiotics covering Pseudomonas species. The extensive use of topical antibiotics and steroids is thought to play a role in the facilitation of fungal proliferation. However, it is still not clear what supports the massive proliferation of fungi in immunocompetent patients. Therefore, the diagnosis in these cases is typically difficult, but should be suspected in those who present with prolonged otorrhea and rapidly progressing audiovestibular symptoms and signs in spite of adequate antibacterial therapy.
Culture
Histopathology
Surgery
Tympanic membrane Cranial nerve Previous history Imaging finding
Age, sex Symptoms
Outcome
Culture Treatment/duration
Surgery Histopathology
A. fumigatus
Fungal hyphae, fibrosis
Debridement
Palsy None Opacified mastoid air cells
Preserved None Clouding of mastoid cavity
Mastoidectomy and debridement Fungal hyphae, necrosis A. flavus
Perforated
62, F Progressive (R) facial weakness, otorrhea
Case 8 [7] 1997
Case 7 [6] 1994
82, M 6 months (L) otalgia, otorrhea, hearing loss Intact
Refused therapy/ unrelated death (HF)
Sequelae/ unrelated death (PNX)
Mastoidectomy Invasive mycotic infection, granuloma Aspergillus sp. Amphotericin B/12 weeks
Palsy Recent diagnosis of MDS Soft tissue mass in R EAC Soft tissue density of R EAC and middle ear Radical mastoidectomy Fungal hyphae, granuloma A. fumigatus Amphotericin B/5 weeks
Palsy None
Perforated
Tympanic membrane Cranial nerve Previous history
Imaging finding
85, M Weeks (R) otalgia, otorrhea, hearing loss Perforated
80, M Progressive external otitis (R)
Case 2 [4] 1988
Age, sex Symptoms
Case 1 [3] 1988
Table I. Characteristics of all patients described in the literature.
–
–
A. flavus
Fungal hyphae, fibrosis
Mastoidectomy
Palsy Diabetes mellitus Erosion of bones
Intact
65, M Otalgia and otorrhea (R)
Case 9 [19] 1997
Unrelated death (MI)
A. fumigatus –
– –
–
– Chronic otitis media
82, M
Case 3 [5] 1990
Fungal hyphae, necrosis A. flavus
Preserved Cholesteatoma Destruction of EAC, densities in mastoid cavity Mastoidectomy
Perforated
52, F (R) otalgia, hearing loss and vertigo
Case 10 [8] 2001
Unrelated death (MI)
A. fumigatus Amphotericin B/50 days
Radical mastoidectomy Necrosis
–
Palsy Cholesteatoma
Perforated
65, F Chronic otorrhea (R)
Case 4 [11] 1993
Case 5 [16] 1993
Fungal hyphae, necrosis Not done
Palsy Diabetes mellitus High signal intensity in middle ear and mastoid Mastoidectomy
Intact
59, M 2 months (R) otalgia, hearing loss
Case 11 [17] 2006
Full recovery
A. flavus Amphotericin B/100 days
Radical mastoidectomy Necrosis, fungal hyphae
OM of skull base mastoiditis
Palsy Diabetes mellitus
Intact
61, F Chronic (R) ear pain
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A. flavus
Not done
(Continued )
Mastoidectomy
Palsy Diabetes mellitus Infiltration of mastoid and base of skull
Intact
65, M Hearing loss, vertigo, otorrhea (L)
Case 12 [18] 2006
Extensive debridement Fungal hyphae, granulation A. flavus Amphotericin B ⫹ hyperbaric O2/1 month, itraconazole 4 months Full recovery
Fluid in mastoid cavity
Preserved Diabetes mellitus
Intact
67, F 4 months (R) otalgia and otorrhea
Case 6 [6] 1994
Aspergillus mastoiditis in an immunocompetent patient 327
Palsy None Abnormal enhancing lesion in IAC Open debridement Fungal hyphae, necrosis Not done Amphotericin B 4 weeks, voriconazole Death from IFI Death (sepsis)
A. fumigatus Amphotericin B
A. fumigatus Topical miconazole/ voriconazole 4 weeks Full recovery
Radical mastoidectomy Fungal hyphae, necrosis
Preserved None Opacified mastoid cells
81, M (R) otalgia, otorrhea, hearing loss Perforated
Case 15 [2] 2009
Negative Itraconazole for 3 months Recovery
Palsy None Opacified mastoid and erosion of bones Radical mastoidectomy Fungal hyphae
67, M Hearing loss and otorrhea (R) Intact
Case 16 [present] 2013
Full recovery
Fluconazole 10 days
Case 4 [11] 1993
Full recovery
Oral itraconazole
Case 5 [16] 1993
Death IFI
Ambisome, itraconazole
Case 6 [6] 1994
EAC, external auditory canal; F, female; HF, heart failure; IAC, internal auditory canal; IFI, invasive fungal infection; L, left; M, male; MDS, myelodysplastic syndrome; MI, myocardial infarction; OM, otitis media; PNX, pneumothorax; R, right.
Outcome
Culture Treatment/duration
Radical mastoidectomy Empyema
Palsy Diabetes mellitus Cerebellar abscesses
Intact
Tympanic membrane Cranial nerve Previous history Imaging finding
Surgery Histopathology
71, F 3 months headache and fever Intact
Case 14 [14] 2008
Case 13 [15] 2007
61, M 1 y (L) hearing loss
Amphotericin B (12 g total)/10 months
Amphotericin B ⫹ hyperbaric O2, 30 days, itraconazole 4 months Full recovery
Amphotericin B ⫹ hyperbaric O2, 13 days, itraconazole 9 months Full recovery Full recovery
Case 3 [5] 1990
Case 2 [4] 1988
Case 1 [3] 1988
Age, sex Symptoms
Outcome
Treatment/duration
Table I. (Continued )
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328 M. Youssef et al.
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Aspergillus mastoiditis in an immunocompetent patient Routine cultures from the ear are not conclusive and do not indicate the real pathogen. Histopathological examination and/or intraoperative cultures are the gold standard. An elevated C-reactive protein and/or erythrocyte sedimentation rate can help in following the clinical course of the infection and response to treatment. Galactomannan antigen can be detected in the serum of patients mainly with hematological malignancies, with an overall sensitivity and specificity for proven invasive aspergillosis of 71% and 89%, respectively. A temporal bone CT scan, bone scanning, and PET scan can aid with the diagnosis. The CT scan is known to be better for bone details and MRI more helpful in delineating the soft tissue abnormalities. The final diagnosis necessitates the demonstration of surgical tissue invasion with Aspergillus species. Aspergillus is usually easily identified by its morphologic appearance, which includes septate hyphae with dichotomotous branching at approximately 45°. Special staining can help to type the organism. Dual arm treatment of Aspergillus mastoiditis is necessary. Aggressive surgical debridement and resection is initially required, followed by antifungal therapy once the diagnosis is confirmed. Amphotericin B used to be the treatment of choice, especially in immunocompromised patients. Voriconazole has become the treatment of choice [20]. Unlike amphotericin B, voriconazole and itraconazole have limited pharmacotoxicity. The optimal dose and duration of therapy are unknown and should be decided by an infectious diseases specialist. The use of hyperbaric oxygen therapy postoperatively has also been reported, but evidence supporting its use is limited [13]. The characteristics of all the cases described in the literature to date are summarized in Table I [2–8,11,14–19]. Included are the age, gender, clinical symptoms, tympanic membrane status, underlying disease, findings of imaging, type of surgery done, histopathological and culture findings, antifungal therapy, and the outcome. We excluded from Table I the 7 cases reported by Varghese et al. since they were summarized in their paper [9]. In almost all cases, the patients were asymptomatic for a long time, and they had received multiple courses of systemic and topical antimicrobials for different alternative diagnoses, including malignant otitis externa, otitis media, and mastoiditis before the correct diagnosis was made. Aspergillus infection progresses slowly over time and the degree of immunosuppression determines the likelihood of manifesting into a disease. All the reported patients were immunocompetent, with no underlying malignancy or HIV, except for 1 patient who had recently been diagnosed with myelodysplasia [3]. A few patients had diabetes mellitus and a few
329
others had underlying ear problems (cholesteatoma or chronic otitis media). Aspergillus species were most commonly A. flavus and A. fumigatus. Old age (average 70 y), a perforated tympanic membrane, and facial nerve involvement were prominent common characteristics. Evidence of facial nerve involvement in patients with mastoiditis, particularly those who do not respond to antibiotics, should raise the suspicion of Aspergillus infection. In most of the reported cases, the patients recovered from the infection. Aggressive surgical debridement with radical mastoidectomy and debridement followed by antifungal therapy was the mainstay of treatment in all of them to ensure the best outcome. Antifungal therapy was usually intravenous amphotericin B for a while, followed by per os itraconazole or voriconazole. In conclusion, this case describes the rare occurrence of fungal mastoiditis in an immunocompetent patient. A high index of suspicion is necessary for early diagnosis. Successful treatment requires a multidisciplinary approach with both surgical intervention and antimicrobial therapy. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
References [1] Petrak RM, Pottage JC, Levin S. Invasive external otitis caused by Aspergillus fumigatus in an immunocompromised patient. J Infect Dis 1985;151:96. [2] van Tol A, van Rijswij J. Aspergillus mastoiditis, presenting with unexplained progressive otalgia in an immunocompetent (older) patient. Eur Arch Otorhinolaryngol 2009;266: 1655–7. [3] Bickley LS, Betts RF, Parkins CW. Atypical invasive external otitis from Aspergillus. Arch Otolaryngol Head Neck Surg 1988;114:1024–8. [4] Cunningham M, Yu VL, Turner J, Curtin H. Necrotizing otitis externa due to Aspergillus in an immunocompetent patient. Arch Otolaryngol Head Neck Surg 1988;114:554–6. [5] Menachof MR, Jackler RK. Otogenic skull base osteomyelitis caused by invasive fungal infection. Otolaryngol Head Neck Surg 1990;102:285–9. [6] Gordon G, Giddings NA. Invasive otitis externa due to Aspergillus species: case report and review. Clin Infect Dis 1994;19:866–70. [7] Bryce GE, Phillips P, Lepawsky M, Gribble MJ. Invasive Aspergillus tympanomastoiditis in an immunocompetent patient. J Otolaryngol 1997;26:266–9. [8] Ohki M, Ito K, Ishimoto S. Fungal mastoiditis in an immunocompetent adult. Eur Arch Otorhinolaryngol 2001;258: 106–8. [9] Varghese R, Nair RM, Kavalakkat FJ. Fungal otomastoiditis: a case series in immunocompetent adults. Indian J Otolaryngol Head Neck Surg 2012:1–4. [10] Amonoo-Kuofi K, Tostevin P, Knight J. Aspergillus mastoiditis in a patient with systemic lupus erythematosus: a case report. J Neurol Surg B Skull Base 2005;15:109–12.
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[11] Hall PJ, Farrior JB. Aspergillus mastoiditis. Otolaryngol Head Neck Surg 1993;108:167–70. [12] Strauss M, Fine E. Aspergillus otomastoiditis in acquired immunodeficiency syndrome. Am J Otolaryngol 1991;12: 49–53. [13] Phillips JS, Jones SE. Hyperbaric oxygen as an adjuvant treatment for malignant otitis externa. Cochrane Database Syst Rev 2005;(2):CD004617. [14] Mani R, Belcadhi M, Ben Said M, Bouzouita K. Aspergillus mastoiditis with intact tympanic membrane in immunocompetent host. B-ENT 2008;4:39–43. [15] Cho YS, Lee DK, Hong SD, Oh WS. Intracranial aspergillosis involving the internal auditory canal and inner ear in an immunocompetent patient. Am J Neuroradiol 2007;28:138–40. [16] Hanna E, Hughes G, Eliachar I, Wannamaker J, Thomford W. Fungal osteomyelitis of the temporal bone:
[17]
[18]
[19]
[20]
a review of reported cases. Ear Nose Throat J 1993;72: 532–41. Kuruvilla G, Job A, Mathew J, Ayyappan AP, Jacob M. Septate fungal invasion in masked mastoiditis: a diagnostic dilemma. J Laryngol Otol 2006;120:250–2. Stodulski D, Kowalska B, Stankiewicz C. Otogenic skull base osteomyelitis caused by invasive fungal infection. Case report and literature review. Eur Arch Otorhinolaryngol 2006;263: 1070–6. Kountakis SE, Kemper JV, Chang J, DiMaio DJ, Stiernberg CM. Osteomyelitis of base of the skull secondary to Aspergillus. Am J Otolaryngol 1997;18:19–22. Herbrecht R, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann JW, et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med 2002;347:408–15.
CASE REPORT
Aspergillus mastoiditis in an immunocompetent patient: A case report and review of the literature
Scand J Infect Dis Downloaded from informahealthcare.com by Nyu Medical Center on 05/13/15 For personal use only.
MONA YOUSSEF1, MARC BASSIM2, NINA SHABB3 & SOUHA S. KANJ1 From the 1Department of Internal Medicine, Division of Infectious Diseases, 2Department of Otolaryngology, and 3Department of Pathology and Laboratory Medicine, American University of Beirut Medical Center, Beirut, Lebanon
Abstract Aspergillus mastoiditis usually occurs in immunocompromised patients. There are a few isolated reports in the literature involving immunocompetent patients. We hereby describe the case of an immunocompetent patient diagnosed with invasive Aspergillus mastoiditis, which was treated successfully, and review the literature pertaining to this condition. The common clinical presentations, putative pathophysiology, and recommended therapy are discussed.
Keywords: Aspergillus, mastoiditis, immunocompetent, otitis
Introduction Aspergillus species can be identified by gross and microscopic appearance as a mold with septate hyphae of 2 to 4 µm in diameter. Human exposure is common, however, human infection is infrequent in immunocompetent patients. Aspergillus mastoiditis is usually reported in cancer patients. We present a case report of Aspergillus mastoiditis in immunocompetent patient who was treated for 6 months before the diagnosis was made by surgery. Case report A 67-y-old man presented with a 6-month history of severe left-sided hearing loss, left tinnitus, and chronic otorrhea from both ears. This was associated with dizziness that had increased in severity over the preceding month, and a chronic headache. He denied fever, chills, or weight loss. He had no respiratory, gastrointestinal, urinary, or dermatologic complaints, and had received topical and systemic antibiotics without improvement. His medical history was otherwise unrevealing. Physical examination revealed whitish debris in both ears and a left facial paralysis. The rest of his
exam was otherwise unremarkable. An audiogram confirmed profound hearing loss in both ears with very poor discrimination. Computed tomography (CT) imaging of the temporal lobes with multiplanar reconstruction showed diffuse opacification of both mastoid air cells, with erosion of the posterior surface of the petrous part of the temporal bone including the posterior half of the inner ear. The erosion pattern included areas of severe bone lysis with segments of diffuse sclerosis (Figure 1A). Magnetic resonance imaging (MRI) showed an erosive and lytic lesion involving the posterior wall of the left petrous pyramid with significant widening of the vestibular aqueduct, erosion of the posterior wall of the superior semicircular canal, and extension into the mastoid air cells with complete opacification of the mastoid air cells, which in view of preserved bony septae suggested retained secretions. An endolymphatic sac tumor was highly suspected. Other diagnoses such as metastatic bone disease and paraganglioma were also considered. A positron emission tomography (PET) scan, ordered to rule out a metastatic origin of this lesion, was negative.
Correspondence: Souha S. Kanj, Division of Infectious Diseases, Department of Internal Medicine, American University of Beirut Medical Center, PO Box 110236, Beirut, Lebanon. Tel: ⫹ 961 3 835845. Fax: ⫹ 961 1 370814. E-mail: [email protected] (Received 22 October 2013 ; accepted 25 October 2013) ISSN 0036-5548 print/ISSN 1651-1980 online © 2014 Informa Healthcare DOI: 10.3109/00365548.2013.867073
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Figure 1. (A) An axial cut from the CT scan of the temporal bone revealing erosion of the posterior wall of the temporal bone and into the labyrinth, with partial erosion of the superior semicircular canal, along with complete opacification of the mastoid. (B) Gomori’s methenamine stain of the surgical specimen: numerous acute angle branching septate hyphae are seen.
Based on the above findings, surgical excision of this mass through a translabyrinthine approach was done. Intraoperative findings revealed a very vascular lesion filling and eroding the mastoid air cells and extending into, and occasionally through, the dura of the posterior fossa and jugular bulb. The lesion was completely excised with no gross residual disease. Intraoperative frozen section specimens were not conclusive. The final pathology result showed severe inflammatory changes with necrosis, bone destruction, and fibrosis, and no evidence of tumor. Numerous acute angle branching septate hyphae were seen, raising the diagnosis of Aspergillus mastoiditis (Figure 1B). A serum sample for Aspergillus galactomannan was also positive, confirming the diagnosis of Aspergillus mastoiditis. Based on the above, the patient was started on itraconazole 200 mg per os twice a day for a total of 3 months. At the 2-month follow-up visit, the patient had markedly improved regarding all his symptoms. Discussion Fungal mastoiditis is an uncommon but serious condition that usually occurs in immunocompromised patients, such as those with leukemia, acquired immunodeficiency syndrome, or diabetes mellitus. The first such case was reported by Petrak et al. in 1985 in an immunocompromised host [1]. The most commonly reported organisms were Mucor and Aspergillus species. A limited number of cases have been reported in immunocompetent adults. In 2009, van Tol and van Rijswijk reported the case of an immunocompetent patient who underwent mastoidectomy because of unexplained, progressive otalgia. Histopathology and cultures yielded Aspergillus fumigatus [2]. Their report also included a review of 6 cases previously
described in the literature [3–8]. All were diagnosed with Aspergillus mastoiditis with no predisposing risk factors. More recently, in 2012, Varghese et al. reported the largest case series of fungal otomastoiditis in immunocompetent adults [9]. Aspergillus infection in the temporal bone can have 1 of 3 different presentations. The most benign form is a non-invasive, localized infection that responds to conservative surgical removal. The second form is an invasive osteolytic presentation, with diffuse granulation tissue and fibrosis, similar to the case described in this report. This is the presentation most commonly reported in immunocompetent patients. The third type, typically presenting in immunocompromised patients, is a fulminant angioinvasive infection with no granulomatous response and very rapid deterioration [10,11]. Four routes of entry of fungal infection to the middle ear are typically discussed: tympanogenic, meningogenic, hematogenic, and nasopharyngeal [1,12]. The patients present frequently with symptoms of intermittent otorrhea, intractable ear pain, chronic dizziness, and progressive cranial nerve palsy. Interestingly, evidence of facial nerve involvement was noted in almost all of the patients [2]. Almost all cases were diagnosed as chronic otitis and mastoiditis with bacterial infections and were treated as such, mainly with topical and systemic antibiotics covering Pseudomonas species. The extensive use of topical antibiotics and steroids is thought to play a role in the facilitation of fungal proliferation. However, it is still not clear what supports the massive proliferation of fungi in immunocompetent patients. Therefore, the diagnosis in these cases is typically difficult, but should be suspected in those who present with prolonged otorrhea and rapidly progressing audiovestibular symptoms and signs in spite of adequate antibacterial therapy.
Culture
Histopathology
Surgery
Tympanic membrane Cranial nerve Previous history Imaging finding
Age, sex Symptoms
Outcome
Culture Treatment/duration
Surgery Histopathology
A. fumigatus
Fungal hyphae, fibrosis
Debridement
Palsy None Opacified mastoid air cells
Preserved None Clouding of mastoid cavity
Mastoidectomy and debridement Fungal hyphae, necrosis A. flavus
Perforated
62, F Progressive (R) facial weakness, otorrhea
Case 8 [7] 1997
Case 7 [6] 1994
82, M 6 months (L) otalgia, otorrhea, hearing loss Intact
Refused therapy/ unrelated death (HF)
Sequelae/ unrelated death (PNX)
Mastoidectomy Invasive mycotic infection, granuloma Aspergillus sp. Amphotericin B/12 weeks
Palsy Recent diagnosis of MDS Soft tissue mass in R EAC Soft tissue density of R EAC and middle ear Radical mastoidectomy Fungal hyphae, granuloma A. fumigatus Amphotericin B/5 weeks
Palsy None
Perforated
Tympanic membrane Cranial nerve Previous history
Imaging finding
85, M Weeks (R) otalgia, otorrhea, hearing loss Perforated
80, M Progressive external otitis (R)
Case 2 [4] 1988
Age, sex Symptoms
Case 1 [3] 1988
Table I. Characteristics of all patients described in the literature.
–
–
A. flavus
Fungal hyphae, fibrosis
Mastoidectomy
Palsy Diabetes mellitus Erosion of bones
Intact
65, M Otalgia and otorrhea (R)
Case 9 [19] 1997
Unrelated death (MI)
A. fumigatus –
– –
–
– Chronic otitis media
82, M
Case 3 [5] 1990
Fungal hyphae, necrosis A. flavus
Preserved Cholesteatoma Destruction of EAC, densities in mastoid cavity Mastoidectomy
Perforated
52, F (R) otalgia, hearing loss and vertigo
Case 10 [8] 2001
Unrelated death (MI)
A. fumigatus Amphotericin B/50 days
Radical mastoidectomy Necrosis
–
Palsy Cholesteatoma
Perforated
65, F Chronic otorrhea (R)
Case 4 [11] 1993
Case 5 [16] 1993
Fungal hyphae, necrosis Not done
Palsy Diabetes mellitus High signal intensity in middle ear and mastoid Mastoidectomy
Intact
59, M 2 months (R) otalgia, hearing loss
Case 11 [17] 2006
Full recovery
A. flavus Amphotericin B/100 days
Radical mastoidectomy Necrosis, fungal hyphae
OM of skull base mastoiditis
Palsy Diabetes mellitus
Intact
61, F Chronic (R) ear pain
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A. flavus
Not done
(Continued )
Mastoidectomy
Palsy Diabetes mellitus Infiltration of mastoid and base of skull
Intact
65, M Hearing loss, vertigo, otorrhea (L)
Case 12 [18] 2006
Extensive debridement Fungal hyphae, granulation A. flavus Amphotericin B ⫹ hyperbaric O2/1 month, itraconazole 4 months Full recovery
Fluid in mastoid cavity
Preserved Diabetes mellitus
Intact
67, F 4 months (R) otalgia and otorrhea
Case 6 [6] 1994
Aspergillus mastoiditis in an immunocompetent patient 327
Palsy None Abnormal enhancing lesion in IAC Open debridement Fungal hyphae, necrosis Not done Amphotericin B 4 weeks, voriconazole Death from IFI Death (sepsis)
A. fumigatus Amphotericin B
A. fumigatus Topical miconazole/ voriconazole 4 weeks Full recovery
Radical mastoidectomy Fungal hyphae, necrosis
Preserved None Opacified mastoid cells
81, M (R) otalgia, otorrhea, hearing loss Perforated
Case 15 [2] 2009
Negative Itraconazole for 3 months Recovery
Palsy None Opacified mastoid and erosion of bones Radical mastoidectomy Fungal hyphae
67, M Hearing loss and otorrhea (R) Intact
Case 16 [present] 2013
Full recovery
Fluconazole 10 days
Case 4 [11] 1993
Full recovery
Oral itraconazole
Case 5 [16] 1993
Death IFI
Ambisome, itraconazole
Case 6 [6] 1994
EAC, external auditory canal; F, female; HF, heart failure; IAC, internal auditory canal; IFI, invasive fungal infection; L, left; M, male; MDS, myelodysplastic syndrome; MI, myocardial infarction; OM, otitis media; PNX, pneumothorax; R, right.
Outcome
Culture Treatment/duration
Radical mastoidectomy Empyema
Palsy Diabetes mellitus Cerebellar abscesses
Intact
Tympanic membrane Cranial nerve Previous history Imaging finding
Surgery Histopathology
71, F 3 months headache and fever Intact
Case 14 [14] 2008
Case 13 [15] 2007
61, M 1 y (L) hearing loss
Amphotericin B (12 g total)/10 months
Amphotericin B ⫹ hyperbaric O2, 30 days, itraconazole 4 months Full recovery
Amphotericin B ⫹ hyperbaric O2, 13 days, itraconazole 9 months Full recovery Full recovery
Case 3 [5] 1990
Case 2 [4] 1988
Case 1 [3] 1988
Age, sex Symptoms
Outcome
Treatment/duration
Table I. (Continued )
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Aspergillus mastoiditis in an immunocompetent patient Routine cultures from the ear are not conclusive and do not indicate the real pathogen. Histopathological examination and/or intraoperative cultures are the gold standard. An elevated C-reactive protein and/or erythrocyte sedimentation rate can help in following the clinical course of the infection and response to treatment. Galactomannan antigen can be detected in the serum of patients mainly with hematological malignancies, with an overall sensitivity and specificity for proven invasive aspergillosis of 71% and 89%, respectively. A temporal bone CT scan, bone scanning, and PET scan can aid with the diagnosis. The CT scan is known to be better for bone details and MRI more helpful in delineating the soft tissue abnormalities. The final diagnosis necessitates the demonstration of surgical tissue invasion with Aspergillus species. Aspergillus is usually easily identified by its morphologic appearance, which includes septate hyphae with dichotomotous branching at approximately 45°. Special staining can help to type the organism. Dual arm treatment of Aspergillus mastoiditis is necessary. Aggressive surgical debridement and resection is initially required, followed by antifungal therapy once the diagnosis is confirmed. Amphotericin B used to be the treatment of choice, especially in immunocompromised patients. Voriconazole has become the treatment of choice [20]. Unlike amphotericin B, voriconazole and itraconazole have limited pharmacotoxicity. The optimal dose and duration of therapy are unknown and should be decided by an infectious diseases specialist. The use of hyperbaric oxygen therapy postoperatively has also been reported, but evidence supporting its use is limited [13]. The characteristics of all the cases described in the literature to date are summarized in Table I [2–8,11,14–19]. Included are the age, gender, clinical symptoms, tympanic membrane status, underlying disease, findings of imaging, type of surgery done, histopathological and culture findings, antifungal therapy, and the outcome. We excluded from Table I the 7 cases reported by Varghese et al. since they were summarized in their paper [9]. In almost all cases, the patients were asymptomatic for a long time, and they had received multiple courses of systemic and topical antimicrobials for different alternative diagnoses, including malignant otitis externa, otitis media, and mastoiditis before the correct diagnosis was made. Aspergillus infection progresses slowly over time and the degree of immunosuppression determines the likelihood of manifesting into a disease. All the reported patients were immunocompetent, with no underlying malignancy or HIV, except for 1 patient who had recently been diagnosed with myelodysplasia [3]. A few patients had diabetes mellitus and a few
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others had underlying ear problems (cholesteatoma or chronic otitis media). Aspergillus species were most commonly A. flavus and A. fumigatus. Old age (average 70 y), a perforated tympanic membrane, and facial nerve involvement were prominent common characteristics. Evidence of facial nerve involvement in patients with mastoiditis, particularly those who do not respond to antibiotics, should raise the suspicion of Aspergillus infection. In most of the reported cases, the patients recovered from the infection. Aggressive surgical debridement with radical mastoidectomy and debridement followed by antifungal therapy was the mainstay of treatment in all of them to ensure the best outcome. Antifungal therapy was usually intravenous amphotericin B for a while, followed by per os itraconazole or voriconazole. In conclusion, this case describes the rare occurrence of fungal mastoiditis in an immunocompetent patient. A high index of suspicion is necessary for early diagnosis. Successful treatment requires a multidisciplinary approach with both surgical intervention and antimicrobial therapy. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
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