American Journal of Otolaryngology–Head and Neck Medicine and Surgery 42 (2021) 102894

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American Journal of Otolaryngology–Head and Neck

Medicine and Surgery
journal homepage: www.elsevier.com/locate/amjoto

Malignant otitis externa: An updated review

José Luis Treviño González *, Laura Lisset Reyes Suárez, Jesús Eduardo Hernández de León
Department of Otolaryngology and Head and Neck Surgery, University of Nuevo Leon, Mexico

A R T I C L E I N F O A B S T R A C T

Keywords: Malignant otitis externa is a progressive infection of the external auditory canal and skull base. Pseudomonas
Malignant otitis externa aeruginosa is the most isolated microorganism and it affects mostly to diabetic, elderly, and immunocompromised
Necrotizing otitis externa individuals.
Skull base osteomyelitis
Non-resolving otalgia and chronic otorrhea are the clinical manifestations presented.
Facial nerve palsy is a common and well recognized complication. (Computed tomography) CT scan is useful
for initial assessment, Technetium-99m is highly sensitive and is part of the protocol for diagnosis.
Treatment should be individualized, with multidisciplinary cooperation among specialties. Management in­
volves systemic antipseudomonal antibiotics and monitoring with radiologic techniques, it also involves the strict
control of diabetes.
It is essential to follow up the patients for at least a year post-treatment. In refractory malignant otitis externa
and affection of facial nerve, surgical management is recommended.
We reviewed the most recent studies on epidemiology, clinical manifestations, diagnosis, and treatment to
provide an update on Malignant Otitis Externa that can offer an overview for clinical practice and future
research.

1. Introduction
Malignant otitis externa (MOE) is an aggressive, highly morbid, and
rarely life-threatening infection of the soft tissues of the external ear and
surrounding structures, which spreads to involve the periosteum and
bone of the skull base. The first reported case was published in 1838 by
Toulmouche and the term “malignant otitis externa” was first used by
Chandler in 1968, because of its high morbidity and mortality before the
introduction of appropriate antibiotic treatment [1].
This infection is mostly seen in immunocompromised patients older
than 65 years of age, especially with diabetes, haematological disorders
(e.g., leukaemia or granulocytopenia) or arteriosclerosis [2].
The most common causative agent remains Pseudomonas aeruginosa,
but other species of bacteria, including methicillin-resistant Staphylo­
coccus Aureus (MRSA), as well as fungal species have been reported.
Common presenting symptoms include otalgia, otorrhea, aural fullness
and hearing loss. Many of the symptoms of otitis externa are also
common to MOE, which can make diagnosis difficult and may lead to a
delay in treatment [3]. The complications most described are osteo­
myelitis, cranial nerve palsy, specially the facial nerve, meningitis, and
brain abscess [4].
The effective treatment of MOE requires an early diagnosis which
demands a high index of suspicion especially at the early stages of the
disease, which is identical to the classic otitis externa.
AlEnazi et al., in 2020, made a survey in which a significant defi­
ciency in the level of knowledge of MOE was found. Therefore, health
education and awareness programs on MOE are recommended [5].
2. Methods
PubMed and GoogleScholar database were searched from January
2016 to October 2020 using the keywords: “malignant otitis externa”/
“necrotizing otitis externa”/“skull base osteomyelitis”. Primary search
thrown 17 articles in the PubMed database and 801 articles in the

Abbreviations: MOE, Malignant Otitis Externa; NOE, Necrotizing Otitis Externa; HIV, Human Immunodeficiency Virus; AIDS, Acquired Immunodeficiency Syn­
drome; MRSA, Methicillin Resistant Staphylococcus aureus; EAC, External auditory canal; 99m-Tc MDP, Technetium 99m-methyl diphosphonate; CT, Computed
tomography; MRI, Magnetic Resonance Imaging; ESR, Erythrocyte sedimentation rate; 18FFDG-PET/CT, 2-deoxy-2-18 fluoro-D-Glucose positron emission
tomography.
* Corresponding author at: Department of Otolaryngology and Head and Neck Surgery, University of Nuevo Leon, Medicine School and University Hospital, Vista
Hermosa, Monterrey, Nuevo Leon, Mexico.
E-mail address: jose.trevinog@uanl.mx (J.L. Treviño González).

https://doi.org/10.1016/j.amjoto.2020.102894
Received 1 December 2020;
Available online 5 January 2021
0196-0709/© 2021 Elsevier Inc. All rights reserved.
J.L. Treviño González et al.
GoogleScholar, those within a range of 5 years prior to the present, in
English or Spanish, with no similar titles or results, were included for our
review’s writing having a total of 31 (Fig. 1).
3. Epidemiology
The annual incidence of the under 18-year age group is the lowest,
while the over 65-year age group is the highest. Older adults are prone to
MOE because they experience a higher frequency of diseases that lead to
an immunocompromised status and infections, such as diabetes mellitus
and chronic kidney disease. Interestingly, it has been found that 27.8%
of MOE cases are comorbid with hypertension, which is in line with
other reports, but it requires further investigation [6].
Bhasker et al. found an increase in the frequency of MOE diagnosis in
Europe over a period of 8 years and 5 months. However, further studies
are required to establish trends nationally because of the serious nature
of the condition [7].
There are no data about incidence of MOE in the world but is
considered infrequent. To this day, there are only series of less than 80
cases that suggest low incidence [8].
4. Etiology and physiopathology
The most common pathogen involved is Pseudomonas aeruginosa,
involved in a high percentage of all cases of MOE (50–90%). Followed by
other pathogen such as Proteus mirabilis, Aspergillus fumigatus, Proteus
spp., Klebsiella spp., and Staphylococci have also been reported [9]. A
high index of suspicion for atypical organisms, such MRSA, should be
maintained in patients with signs and symptoms of MOE who do not
have diabetes [10].
Diabetes mellitus has been thought to predispose patients to MOE by
inducing microangiopathy in the ear canal and hampering chemotaxis of
white blood cells resulting in increased susceptibility to infection [11].
MOE typically starts in the external auditory canal (EAC) and spreads
to the stylomastoid foramen and then to the mastoid tip and the jugular
foramen. Finally, the septic process extends to the petrous apex and the
middle cranial fossa [12].
Kwon et al., described four spreading patterns of the soft tissue
extension: medial, anterior, crossed and intracranial spreading, best
described in Table 1.
One of the severe complications that MOE can result in is the cranial
nerve involvement, especially the facial nerve [13].
Fig. 1. Review flowchart.
2
American Journal of Otolaryngology–Head and Neck Medicine and Surgery 42 (2021) 102894
Table 1
Spreading patterns of the soft tissue extension, as described by Kwon et al.
Spreading Soft tissue extension
patterns
Medial Ipsilateral nasopharyngeal wall thickening and/or ipsilateral
preclival soft tissue infiltration
Anterior Extension and involvement of the masticator space and/or
condylar bone marrow infiltration.
Crossed Contralateral nasopharyngeal wall is thickened with
contralateral preclival soft tissue infiltration.
Intracranial Dural enhancement present in the intracranial compartment.
5. Risk factors
The most common reported risk factor in the literature for devel­
oping MOE is diabetes mellitus (DM), with an estimated 90–100% of
patients with MOE having DM. Another major risk factor is immuno­
suppression, such as patients suffering from Human Immunodeficiency
Virus (HIV), transplant patients, or patients with advanced cancer. MOE
should always be suspected when patients with immunosuppression
present with symptoms of otitis externa, especially if otitis is not
responding to typical therapy. Several studies have found that advanced
age is another important factor [14].
Nearly 20% of patients do not have such past medical history. In
2019, Bruschini et al. reported a patient that unlike most of the affected
subjects, was neither diabetic nor immunocompromised, but had been
previously treated with radiotherapy in the head and neck region 20
years before the presentation of MOE. Radiotherapy may induce a very
slow process of necrosis in the bone and bacterial infection could have
invaded the necrotic tissue [15,16].
6. Clinical presentation
This condition frequently presents as non-resolving otalgia, which is
often severe, radiating to the ipsilateral face [17]. Clinical manifesta­
tions of the disease persist for longer than one-month, including chronic
otorrhea, headache and cranial nerve involvement [18].
Singh et al. showed in 2018 that nocturnal pain is the most common
presenting feature, followed by ear discharge, hearing loss and tempo­
romandibular joint pain [19].
Otoscopy may reveal edema of the EAC and the presence of granu­
lation tissue or polyp of the EAC floor near the junction of the osseus and
cartilaginous portions [20] (Fig. 2).
Cranial nerve paralysis at disease presentation has been reported and
J.L. Treviño González et al.
Fig. 2. Granulation tissue in external auditory canal by otoscopy.
well recognized as a complication, of which the facial nerve is most
involved since it is near the external auditory canal. This factor increases
mortality by 50% [21].
Undiagnosed or partially treated MOE can progressively spread to
the skull base and cause major complications such as thrombosis of
lateral sinus or internal jugular vein, meningitis, Bezold’s abscess and
paralysis of cranial nerves [22].
7. Diagnosis
The MOE diagnosis is generally established from a range of clinical,
laboratory and radiographic findings. When a patient with diabetes
complains of otalgia or otorrhea, and physical examination shows
swelling of the ear canal or granulation growth, physicians should
consider the possibility of MOE [9].
In 1987, Cohen and Friedman described diagnostic criteria for NEO
including: 1) typical signs and symptoms such as otalgia, otorrhea,
edema, and granulation tissue; 2) patient characteristics of old age and
diabetes mellitus, and 3) imaging findings that include positive bone
scan with methylene diphosphonate (MDP)-technetium-99m (Tc99m)
as a major criterion and positive radiography as minor.
Inflammatory markers, such as erythrocyte sedimentation rate
(ESR), white blood cell count or C- reactive protein (CRP) may be
increased in patients with MOE [18].
Computed tomography (CT) scan has been proven a useful tool for
diagnosis and prognosis prediction. Magnetic resonance imaging (MRI)
is useful for soft tissue involvement, but it is less adequate for bone
involvement, expensive, and not available at all centers [23]. Magnetic
resonance imaging provides excellent anatomical localization and soft
tissue involvement in the setting of suspected osteomyelitis. Bone
changes may be detected as early as 3–5 days from disease onset. The
sensitivity of MRI in the detection of diabetes osteomyelitis has been
reported to be 90%, with a specificity of 79% [24].
Traditional nuclear medicine studies were promoted throughout the
1980s as a preferred imaging modality for diagnosis and managing MOE
patients, but the utility of Tc99m and Ga67 studies as the standard for
the diagnosis and monitoring of MOE has recently been drawn into
question [25,26].
The protocol for diagnosis included a Tc99m, which is highly sen­
sitive, followed by a Galium-67 scan, which is useful in deciding the end
point of antibiotic therapy for MOE. The combination of these two tests
was shown to be more sensitive and specific for diagnosing MEO than
was any other available test.
Positron emission tomography (PET) with 2-deoxy-2-[fluorine-18]
fluoro-D-glucose integrated with CT (18FFDG-PET/CT) is a modality in
3
American Journal of Otolaryngology–Head and Neck Medicine and Surgery 42 (2021) 102894
which PET and CT are simultaneously acquired and combined into a
single image, and was found to have a sensitivity of 96% and a speci­
ficity of 91%, with the highest accuracy for confirming or excluding
osteomyelitis compared to all other modalities [23].
The combination of radiologic and radionuclide studies plays a
crucial role in the initial diagnosis and follow-up of patients.
8. Treatment
Prior to the introduction of anti-Pseudomonas aeruginosa antibiotics
mortality was as high as 67% and surgery was considered the main
treatment modality [27]. Malignant otitis externa requires conservative
management and ESR proved to be a good indicator of treatment
response. Once the offending pathogen has been isolated, treatment is
tailored, based on the pathogen’s antibiotic profile. Although diabetes is
the most important risk factor for the development of NEO, there are
limited data regarding the correlation between diabetes severity and
disease extent [18,24].
The use of oral and topical fluoroquinolones in systemic and targeted
treatment has allowed for effective outpatient treatment and has
decreased the need for hospitalization [28]. Treatment with a length of
4–6 weeks may be inadequate for patients at high risk of recurrent in­
fections, such as those with infection because of MRSA and end-stage
renal disease. Nonetheless, the optimal length of therapy for osteomy­
elitis in MOE remains unclear [29].
Third generation cephalosporins with anti-pseudomonal activity
must be consider in cases of ciprofloxacin resistance. The combined use
of semisynthetic penicillin and aminoglycoside is only recommended if
multi-resistance is shown in antibiogram [30]. Temporomandibular
joint involvement also is said to be rare and associated with poor
prognosis. To ease with the temporomandibular joint symptoms, muscle
relaxants are a good option [18].
As MOE can reoccur as long as one year after treatment is completed,
it is essential to follow these patients up for at least a year post-treatment
[27]. Periodic nuclear imaging has been recommended for evaluating
treatment response.
Inflammatory markers, such as leukocyte count sedimentation rate
and C-reactive protein, combined with periodic physical examinations,
may also be used for assessing disease progression [26]. Gallium scan is
the imaging of choice for follow-up, since it returns to normal once
inflammation subsides [21].
Surgery must be considered in cases of aggressive or advanced dis­
ease, facial nerve paralysis, deep tissue sterile culture and refractory
MOE, Refractory MOE is defined as no clinical improvement after six
weeks of conventional treatment [19]. Extensive bone erosion requires
Canal wall up (CWU) mastoidectomy as the minimal surgical procedure
and should be converted to Canal wall down (CWD) mastoidectomy in
cases of sever bone erosion of the posterior canal wall and when better
exposure of the middle ear is required [27]. Surgery reduces local
infective load, removes necrotic tissue, and allows formation of new
tissue growth, which increase local vascularity allowing systemic anti­
biotics to reach the required area [31].
The treatment regimen should be individualized, with multidisci­
plinary cooperation among specialties, including endocrinology, inter­
nal medicine and infectiology.
9. Conclusions
Malignant otitis externa is a progressive infection of the external
auditory canal and skull base. Elderly patients, diabetes, immunosup­
pression (including chemotherapy, HIV/AIDS, or malnutrition) are
important risk factors. Being diabetes the most relevant for this condi­
tion by increasing susceptibility to infection. Pseudomonas aeruginosa is
commonly the pathogen involved. But it can also be caused by other
microbiological agents such as Staphylococcus aureus, Coagulase-negative
species, and other fungal organisms. MOE typically presents as non-
J.L. Treviño González et al.
resolving severe otalgia, with ear discharge, headache, hearing loss and
even affection of the facial nerve. Diagnosis must be established with
clinical, laboratory and radiographic findings. It is necessary to look for
malignant otitis externa in uncontrolled diabetic patients, to treat them.
Finally, management must include systemic antibiotics and strict control
of diabetes. In cases of refractory malignant otitis externa, surgical
debridement is strongly recommended to relieve nocturnal pain. It also,
is important to evaluate treatment response. Treatment should always
be individualized, with multidisciplinary cooperation among specialties.
Future investigation on epidemiology on Malignant Otitis Externa is
recommended because there is no sufficient data about incidence
globally or in different countries.
Health education, awareness programs and further investigation on
Malignant Otitis Externa are recommended.
Funding
No funding to declare.
Ethical approval
No ethical approval was obtained.
Informed consent
Informed consent not required.
Declaration of competing interest
Author declares that there is no conflict of interest regarding the
publication of this article.
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