6

Chia-Lin Lee et al
7
Case Report
Malignant Otitis Externa in Patients with Diabetes Mellitus
Po-Yu Liu
1
, Zhi-Yuan Shi
1,2
, Wayne Huey-Herng Sheu
2,3,4

Abstract
People with diabetes mellitus can be more prone to infections. Conspicuous immune deficits are
common in diabetic mellitus and are held responsible for increasing rate and severity of infection in di-
abetic patients. Malignant otitis externa is one of the potentially life-threatening infections in patients
with diabetes mellitus. The causative pathogen is Pseudomonas aeruginosa in most cases. Granulation
tissue in the floor of the auditory canal is frequent seen. Despite increasing reports of HIV-associated
malignant otitis externa, which characterized by its younger, less granulation tissue in the ear canal
and less fungal infections, diabetes mellitus remains the most common predisposing condition. Thus,
malignant otitis externa should be considered in elderly diabetic patients present with severe otalgia.
Treatment delay results in cranial neuropathies and skull base infection.
(Formos J Endocrin Metab 2012; 3(1): 7-13)
Key words: Malignant otitis externa, pseudomonas, sepsis, diabetes mellitus, antimicrobial therapy
1
Section of Infectious Diseases, Department of Internal Medicine, Taichung Veterans General Hospital,
2
School of Med-
icine, National Yang Ming University,
3
Division of Endocrinology and Metabolism, Taichung Veterans General Hospi-
tal,
4
Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
Correspondence to: Wayne Huey-Herng Sheu, MD, PhD, Division of Endocrinology and Metabolism, Department of
Internal Medicine, Taichung Veterans General Hospital, No. 160, Section 3, Chung-Kang Road, Taichung, Taiwan 407, ROC
Tel: 886 4 23741300 fax: 886 4 23502942 E-mail:whhsheu@vghtc.gov.tw
Introduction
Diabetes mellitus is a common risk factor for
many infections. Some specific infections develop
almost exclusively in these patients. Many infections
occur with increased mortality and are associated
with an increased risk of complications in patients
with diabetes.
1
Malignant otitis externa , named
by Chandler
2
who reported the first case series, is
one of the potentially life-threatening infections in
diabetic patients. It is an invasive infection of the
external auditory canal with eventual extension to
the middle ear, mastoid air cells, and temporal bone.
On the other hand, some authors suggested using the
term necrotizing otitis externa, since the pathogenic
process is not neoplastic.
3
In this review, we use the
term malignant otitis externa because it is used more
frequently in the literatures. The mortality rate of
malignant otitis externa was high before the inven-
tion of effective antimicrobial treatment. Now, it can
be successfully treated medically in most patients.
Early diagnosis and optimal treatment markedly im-
prove the patient's outcome.
Epidemiology
Although any condition causing immunosup-
pression, such as HIV/AIDS, chemotherapy, hema-
tological malignancy, splenectomy, and organ trans-
plantation, may predispose a patient to malignant
otitis externa, the infection is traditionally consid-
ered a disease of diabetes mellitus
4
. Earlier research
showed that the prevalence of diabetes mellitus in
malignant otitis externa is about 90% to 100%
2, 5, 6

8
Po-Yu Liu et al
Formos J Endocrin Metab Vol. 3 No. 1: 7-13 9
Malignant otitis externa in diabetics
with most of the patients being the elderly. Reported
tcases in Taiwan had generally showed similar epi-
demiologic features. However, the epidemiology of
malignant otitis externa has changed in the past de-
cade. There are increasing reports of malignant otitis
externa in patients with AIDS.
4
AIDS patients who
have malignant otitis externa are younger than the
typical elderly patient with this potentially fatal in-
fection, and most of the infected AIDS patients have
no diabetic history. The most common pathogen
isolated from the aural drainage in malignant otitis
externa is Pseudomonas aeruginosa followed by
Staphylococcus aureus.
2
Fungus, especially Aspergil-
lus fumigatus, is found more commonly in patients
who have HIV than in those who have diabetes mel-
litus.
7,8
The typical granulation tissue along the floor
of the external auditory canal in most malignant oti-
tis externa may also be absent in patients with HIV
infection.
9
The 80% mortality rate in the 1950s has
been dramatically decreased to 5% with earlier di-
agnosis, surgical intervention, antimicrobial therapy,
and management of underlying conditions.
10

Malignant otitis externa is rarely reported in
children, only in few cases including IgG subclass
deficiency, IgA deficiency, acute monocytic leuke-
mia, post chemotherapy, and bone marrow transplan-
tation.
11
Diabetes mellitus is less common in children
with malignant otitis externa; one review suggests
that only 21% of children with malignant otitis exter-
na also have diabetes mellitus.
12
P. aeruginosa is also
the most common causative pathogen in children.
Pathophysiology
In general, several aspects of host defense re-
sponses are altered in patients with diabetes mellitus,
including innate immunity and adaptive immunity.
In diabetes mellitus patients, endothelial dys-
function leads to vasoconstriction instead of the
usual local vasodilation in inflammation.
13,14
This
phenomenon could potentially decrease the ability of
phagocytes to leave the bloodstream and enter the in-
fected tissues. Previous study suggested that dysreg-
ulation of nitric oxide production and blunted nitric
oxide responses to bradykinin are the causes of en-
dothelial cell dysfunction.
15
The polymorphonuclear
function is depressed, particularly when acidosis is
also present. Chemotaxis, adherence, phagocytosis,
and intracellular killing may be affected.
16-18
There is
evidence that insulin optimizes polymorphonuclear
neutrophil functions and improves chemotaxis.
19,20

and some studies suggest that diabetic patients has
imparied phagocytosis.
21,22

Although the disease has been described for
decades, little is known about the pathophysiology.
Bernheim described the lesions of the skin cover-
age of the external ear canal in malignant external
otitis as inflammation of the epidermis with acute
and chronic inflammatory reaction in the dermis.
23

Bacteria invasion of vessel walls causing vasculitis
with thrombosis and coagulation necrosis of sur-
rounding tissue are common pathologic findings.
2

Water exposure such as irrigation for cerumen dis-
impaction in elderly diabetic patients is a proposed
factor of malignant otitis externa.
24
In Taiwan, swim-
ming may cause ear infection, as said in a review by
Wang et al, especially acute diffuse otitis externa.
25

Another research reported that a contributing factor
is the increased pH of cerumen in diabetic patient.
26

Microangiopathy from diabetes mellitus and ageing
have also been suggested to predispose elderly dia-
betic patients to malignant otitis externa.
11

The infection often originates from the exter-
nal auditory canal and then spreads to the skull base
through the fissures of Santorini. Bone destruction
and progressive spread s of infection to skull base
foramina cause cranial neuropathies. The most com-
monly affected nerve is the facial nerve due to the
vicinity of the stylomastoid foramen to the external
auditory canal.
11
Meningitis and brain abscess may
develop as a consequence of the infection as it ex-
tends into the sigmoid sinus, leading to septic throm-
bosis of the sigmoid sinus and internal jugular vein.
3

It may also result in thrombosis of the carotid artery
ensuing in brain infarction. Skull base osteomyelitis
can spread to the contralateral side, affecting the
contralateral cranial nerves and involve the cervi-
cal spine.
27,28
Fungal malignant otitis externa often
originates in the middle ear or mastoid in contrast to
Pseudomonal malignant otitis externa.
8
Po-Yu Liu et al
9
Malignant otitis externa in diabetics
Formos J Endocrin Metab Vol. 3 No. 1: 7-13
Microbiology
Pseudomonas aeruginosa, a gram-negative ob-
ligate aerobe rod, is the causative organism in more
than 98% of patients with malignant otitis externa.
29
Pseudomonas aeruginosa is not a part of normal ear
canal flora, thus isolation of Pseudomonas aerugi-
nosa is indicative of the infection. While Staphylo-
coccus aureus, Klebsiella species, Staphylococcus
epidermidis, and rarely Aspergillus fumigatus have
been reported to cause malignant otitis externa, some
experts argue that some of these organisms may
have been colonizers and not true pathogens.
11
More
than 70 % isolates are Staphylococcus species and
Pseudomonas aeruginosa in a bacteriologic study
performed in Taiwan.
30
The majority of malignant
otitis externa are mixed infections, but for 30% of
patients Pseudomonas aeruginosa is the only organ-
ism isolated from aerobic cultures.
Fungus can cause malignant otitis externa, es-
pecially in immunocompromised patients other than
diabetes mellitus. The most common isolated fungal
organism is Aspergillus fumigatus. Other fungus,
including Aspergillus flavus, Aspergillus niger, and
Scedosporium apiospermum have been isolated from
patients with malignant otitis externa.
11
Pseudomonal
malignant otitis externa in patients with HIV occur
correspondingly with CD4 levels of less than 100
cells/mm and Aspergillus-associated malignant otitis
externa with CD4 counts less than 50 cells/mm.
11
Clinical Manifestation
Patients may present severe persistent otorrhea
and otalgia. The otalgia may worsens at night and is
unresponsive to topical medications commonly used
for otitis externa. The otalgia may be lancinating in
nature.
29
The pain often extends to the temporoman-
dibular joint, accompanied with hearing impairment
and headache. Otoscopy may reveal polypoid granu-
lation tissue in the floor of the auditory canal, espe-
cially at the bone-cartilage junction.
31,32
The external
canal may be tender on palpation and the pinna is
often painful when pulled on. Some patients have
exudate. The tympanic membrane may be normal or
ruptured. Systemic symptoms such as fever may be
absent and white blood cell count and differential are
usually normal.
Facial palsy is the most common cranial neu-
ropathy and may appear early in the course of the
disease. Disease progression may result in involve-
ment of the glossopharyngeal, vagal, spinal acces-
sory, hypoglossal, trigeminal, and abducens nerves.
Extension to the petrous pyramid can cause Gradeni-
go's syndrome, as trigeminal and abducens nerve
palsies.
Complications include osteomyelitis of the
skull base, involvement of temporomandibular joints
and cranial nerve palsies. Rarely occurred but fatal
central nervous system complications include men-
ingitis, brain abscess, and dural sinus thrombophle-
bitis. Of the cranial nerves, facial nerve is the most
commonly involved, followed by the glossopharyn-
geal, vagal, and spinal accessory nerves at the jugu-
lar foramen, and the hypoglossal nerve as it exits the
hypoglossal canal. Trigeminal, abducens, and very
rarely optic nerve may also be involved.
4
The pres-
ences of cranial nerve palsies, such as facial nerve
palsy, indicate a poor prognosis. The intracranial
complications are the most frequent cause of death.
Diagnosis
Malignant otitis externa is more frequently di-
agnosed by a generalist physician with a high index
of suspicion than any other speciality.
4
Currently, no
single diagnostic criterion exists for malignant otitis
externa. The diagnosis is made based on a combina-
tion of clinical, laboratorial, and radiographic find-
ings. Because most affected patients have diabetes,
the internist is usually the first physician to see the
patient with uncontrollable earache.
4
An elderly
diabetic patient presents with severe otalgia accom-
panied by otorrhoea must be under the suspicions
of malignant otitis externa until proved otherwise.
Junaid Bajwa proposed an algorithm for the manage-
ment of patients with symptoms and signs of otitis
externa in primary care (Figure 1) and suggests early
consultation with an otolaryngologist when malig-
nant external otitis is suspected.
10
Po-Yu Liu et al
Formos J Endocrin Metab Vol. 3 No. 1: 7-13 11
Malignant otitis externa in diabetics
The ESR is invariably high and can be used to
monitor disease activity.
29
A positive bone scanning
(technetium 99 m) can be presumptive diagnosis of
malignant external otitis but in patients with otitis
externa the results would also be positive. Gallium
scans are more specific.
32
Computed tomography and
magnetic resonance imaging are better for demon-
strating temporal involvement, osteomyelitis, and
abscess formation.
33,34

Culture of drainage fluid and biopsy from
external ears provide a microbiologic diagnosis.
Histopathologic examination of the granulation tis-
sue from the infection site is helpful in establishing
diagnosis and eliminating other possible differential
diagnoses such as epidermal carcinoma. Although
malignant external otitis seems to be uncommon in
AIDS patients, the diagnosis should also be consid-
ered in any patient who presents painful otorrhoea
and the symptoms persist despite receiving treatment
for simple external otitis
Modified from InnovAiT, 2009
Figure 1. Management of otitis externa in primary care.
10
Po-Yu Liu et al
11
Malignant otitis externa in diabetics
Formos J Endocrin Metab Vol. 3 No. 1: 7-13
Treatment
Systemic antipseudomonal antibiotics is the
mainstay of treatment.
36
Topical therapy is not help-
ful. Generally, a 6- to 8-week treatment is recom-
mended when -lactams are used, or as indicated by
the results of clinical response and radiologic inves-
tigation. Oral ciprofloxacin has been used with vary-
ing durations from 8 weeks to 6 months. Serial ESR
measurements have been used to follow the progress
of treatment and in selecting an end point for the
length of therapy. There is no comparative study on
the relapse rates between treatment with -lactams
or ciprofloxacin, but relapses can develop up to 1
year after end of therapy.
Although oral fluoroquinolones have been the
drug of choice for many years, recently increasing
resistance by P. aeruginosa is noted.
5,6,36,37
Patients
should be monitored closely when treated with
fluoroquinolones. Severe infection with resistant P
aeruginosa generally needs debridement and pro-
longed course of parenteral antibiotics including an
antipseudomonal -lactam agent with or without an
aminoglycoside.
4
Strict glycemic control is very important during
acute infection or high stress state, due to the risk of
acute metabolic decompensation during infections
which may result in prolonged hospital stays and ad-
ditional financial burden.
Although extensive surgical treatment was nec-
essary before the era of effective antibiotic therapy,
2

the role of surgical treatment for this disorder is now
limited to diagnostic confirmation or debridement of
the ear canal, including necrotic cartilage, bone and
granulation tissue.
10,39
Some experts use hyperbaric
oxygen in refractory cases as an adjuvant therapy,
but the efficacy has not yet been proved.
39,40

Often antibiotic dosage adjustments are needed
in patient with diabetes mellitus or the elderly be-
cause of reduced hepatic metabolism, altered renal
function and fluid electrolyte status.
41
These factors
also make them more likely to have adverse effects
from antibiotics. Close monitoring is needed in treat-
ing these patients.
Several areas need further study of appropri-
ate duration of antimicrobial therapy. The impact
of prolonged therapy may increase the incidence of
resistant organisms. However, the duration of anti-
microbial therapy is largely dependent on adequate
source control.
With regard to high-risk patients, especially
those complicated with central nervous system infec-
tion, poor clinical outcomes are still noted. Due to
the infrequency of these patients, prospective ran-
domized control trials are unlikely to be performed;
therefore, other types of studies, including prospec-
tive observational studies, may be useful.
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