eMedicine Specialties > Otolaryngology and Facial Plastic Surgery > External Ear Diseases

External Ear, Malignant External Otitis

Background
Toulmouche was probably the first physician to report a case of malignant external otitis (MEO), in 1838. In 1959, Meltzer reported a case of pseudomonal osteomyelitis of the temporal bone. In 1968, Chandler discussed the clinical characteristics of malignant external otitis (MEO) and defined it as a distinct clinical disease.1 He described this external otitis as malignant because he observed an aggressive clinical behavior, poor treatment outcome, and a high mortality rate for the patients affected by this disease. The subsequent development of effective antibiotics for treating pseudomonal infections has improved the treatment outcomes for patients with malignant external otitis (MEO). Thus, some physicians have suggested that the term malignant should be abandoned in order to provide a more accurate description of the disease process.

Anatomy of the ear.

Pathophysiology
Malignant external otitis (MEO) is an infection that affects the external auditory canal and temporal bone. The causative organism is usually Pseudomonas aeruginosa, and the disease commonly manifests in elderly patients with diabetes. The infection begins as an external otitis that progresses into an osteomyelitis of the temporal bone. Spread of the disease outside the external auditory canal occurs through the fissures of Santorini and the osseocartilaginous junction.

Frequency
United States

Malignant external otitis (MEO) is more common in humid and warm climates than in other climates.

Mortality/Morbidity

Cranial neuropathy o Cranial nerves can be affected by inflammation along the skull base or by a neurotoxin produced by Pseudomonas species. The facial nerve (VII) is affected

most commonly, usually at the stylomastoid foramen. As the disease progresses, cranial nerves IX, X, and XI can be affected at the jugular foramen, followed by XII at the hypoglossal canal. Cranial nerves V and VI can be affected if the disease extends to the petrous apex. In 1977, Chandler reported a 32% incidence of facial nerve paralysis.2 The incidence

of facial nerve paralysis appears to have decreased with the development of more effective medical therapy as shown by Franco-Vidal et al who reported a 20% incidence of facial nerve paralysis in 46 treated patients.3 The other cranial nerves are affected less frequently than the seventh cranial nerve. The development of cranial neuropathy generally was thought to reflect advanced-stage disease associated with a worse prognosis. More recently, Corey et al, Soudry et al, and Mani et al suggested that the presence of facial nerve paralysis does not worsen the prognosis.4,5 Recovery of facial nerve function is poor and unpredictable, and should not be used as an indicator of successful treatment. Other cranial nerves that are affected have a higher rate of recovery. Intracranial complications: These complications rarely occur in the absence of cranial nerve palsies. Meningitis, brain abscess, and dural sinus thrombosis may ensue. Cranial neuropathies related to the jugular foramen should raise concern for sigmoid sinus thrombosis. Cavernous sinus thrombosis should be considered if cranial nerves V or VI are affected. Intracranial complications reflect severe disease and are commonly fatal. Comorbid conditions: Patients with malignant external otitis (MEO) almost always have diabetes, often with other multiple medical problems. During the course of therapy, Chandler found some deaths related to pneumonia, uremia, myocardial infarction, strokes, and liver failure. Franco-Vidal showed that patients with systemic immunodeficiencies had a worse prognosis.3

Sex
Malignant external otitis (MEO) is more common in males than in females.

Age
Malignant external otitis (MEO) has been reported in all age groups but is most common in patients who are elderly (age, >60 y).

Clinical
History

Diabetes (90%) or immunosuppression (illness or treatment related) Severe, unrelenting, deep-seated otalgia Temporal headaches Purulent otorrhea Possibly dysphagia, hoarseness, and/or facial nerve dysfunction

Physical

Inflammatory changes are observed in the external auditory canal and the periauricular soft tissue.

The pain is out of proportion to the physical examination findings. o Marked tenderness is present in the soft tissue between the mandible ramus and

mastoid tip. Granulation tissue is present at the floor of the osseocartilaginous junction. This

finding is virtually pathognomonic of malignant external otitis (MEO). Otoscopic examination may also reveal exposed bone. The cranial nerves (V-XII) should be examined. Mental status examination should be performed. Deterioration of the mental status may indicate intracranial complication. The tympanic membrane is usually intact. Fever is uncommon.

Causes

Diabetes (90% of patients) o Diabetes is the most significant risk factor for developing malignant external otitis

o o o o

(MEO). Small-vessel vasculopathy and immune dysfunction associated with diabetes are primarily responsible for this predisposition. The cerumen of patients with diabetes has a higher pH and reduced concentration of lysozyme, which may impair local antibacterial activity. No difference in predisposition is found between diabetes types I and II. The predisposition is not necessarily related to the severity of glucose intolerance or

periods of hyperglycemia. Immunodeficiencies, such as lymphoproliferative disorders or medication-related immunosuppression AIDS o Malignant external otitis (MEO) associated with AIDS may have a different

o o o o

pathophysiology than classic malignant external otitis (MEO). Patients present with similar symptoms but are generally younger and do not have diabetes. Granulation tissue may be absent in the external auditory canal. Pseudomonas is not necessarily the dominant causative organism. Patients with AIDS generally have a poorer outcome than patients with diabetes.

Aural irrigation: As many as 50% of cases of malignant external otitis (MEO) have been reported to be preceded by traumatic aural irrigation in patients with diabetes.

Differential Diagnoses
Malignant Tumors of the Temporal Bone

Workup
Laboratory Studies

Leukocyte count o The leukocyte count is usually normal or mildly elevated. o A left shift is not commonly found.

Erythrocyte sedimentation rate o Erythrocyte sedimentation rate (ESR) is invariably elevated, with an average of 87

o o

mm/h. It begins to decrease within 2 weeks of initiating therapy but takes many months to return to normal. ESR can be used to support the clinical diagnosis since acute external otitis or ear

canal malignancy usually does not cause a rate elevation in this lab test. Serum chemistry o Patients with known diabetes need an evaluation of the serum chemistry to determine

if the infection is affecting their baseline glucose intolerance. Patients without a history of diabetes should be tested for glucose intolerance.

Culture and sensitivities from the external auditory canal o Culture from the ear drainage should be performed ideally before antimicrobial

therapy is initiated. The most common causative organism is P aeruginosa (95%). This organism is an aerobic, gram-negative rod. Pseudomonas species has a mucoid coating that deters phagocytosis. Exotoxins (ie, exotoxin A, collagenase, elastase) can cause tissue necrosis, and some strains produce a neurotoxin that may be partially responsible for cranial neuropathies. Less common organisms identified include Aspergillus and Proteus species, Candida species, Staphylococcus aureus, and Staphylococcus epidermidis.

Imaging Studies

These are important adjuncts for determining the presence of osteomyelitis, the extent of disease, and response to therapy. Technetium Tc 99 methylene diphosphonate bone scanning is based on binding to osteoblasts. o This scan depicts as little as a 10% increase in osteoblastic activity. However, this test is not specific since tumors or bony dysplasias, in addition to osteomyelitis, can cause osteoblastosis. It is useful in the initial evaluation because a positive finding in the correct clinical context can lead to confirmation of the diagnosis. The test is not useful for assessing the response to therapy since results remain persistently positive long after clinical improvement because of continuous bone remodeling and reformation. This test may also have limited usefulness for patients with a prior history of mastoiditis or otologic surgery. The application of single-photon emission computed tomography (SPECT)

o o

o o

technology has improved the poor spatial resolution traditionally associated with this test. Gallium citrate Ga 67 scan is very sensitive but is not specific because gallium binds to actively dividing cells, including inflammatory cells, tumor cells, and osteoblasts. o Uncertainty is possible regarding whether a positive test result represents an

inflammatory condition, soft tissue, or bone disease. This test is most helpful when used as a monitor of successful treatment. Improvement of a positive test result correlates with therapeutic response.

o o

A baseline test is usually obtained at the initial diagnosis for comparison with followup studies during treatment. A quantitative comparison of the lesion to the nonlesion side may improve the interpretation of these studies for distinguishing acute external otitis from malignant external otitis (MEO) and for determining the efficacy of therapy. The application of SPECT technology has improved the poor spatial resolution

traditionally associated with this test. Indium In 111labeled leukocyte scan attempts to provide the same sensitivity as a gallium citrate Ga 67 scan but is more specific to an inflammatory process. o It does not appear to provide an improvement in scintigraphic technique for helping to

o o

establish the diagnosis. It may be better than gallium citrate Ga 67 scans for assisting in establishing the correct timing of disease resolution. This test can be unreliable for imaging chronic osteomyelitis in other areas of the

body. Thus, the accuracy of this application needs further study. CT scanning and MRI are both useful for evaluating the anatomic extent of soft tissue inflammation, abscess formation, and intracranial complications. o CT scanning fails to diagnose early osteomyelitis because 30-50% of bone

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destruction is required to detect osteomyelitis by CT scanning. MRI provides poor bone resolution. The soft tissue manifestations regress on CT scanning and MRI with response to therapy. Bone changes remain persistently abnormal on CT scans for at least one year and are not well demonstrated by MRI studies. Thus, neither of the tests can be used to determine osteomyelitis resolution. Most authors advocate obtaining a CT scan with the initial evaluation for all patients, whereas Benecke advocates obtaining this test selectively for patients with cranial neuropathy, extensive bone changes on technetium scan, or poor clinical response to treatment. Grandis et al and Okpala et al support obtaining a CT scan early in the diagnostic/treatment algorithm. Peleg et al showed that there is a correlation between clinical course and the extent of anatomical areas involved as measured on initial CT scan findings.6 MRI and CT scanning are equally sensitive in detecting the soft tissue extent of the disease, but MRI is more sensitive for detecting intracranial complications.

Procedures

Obtain a biopsy of the external auditory canal to exclude carcinoma or other etiologies.

Histologic Findings
Nadol described the histopathology of 2 temporal bones affected by malignant external otitis (MEO). The infection did not spread through the pneumatized air tracts of the temporal bone. Rather, it spread along the vascular and fascial planes on exiting the temporal bone through the external auditory canal osseocartilaginous junction or fissures of Santorini. The otic capsule appeared to be resistant to the disease process. Linthicum described histopathologic findings in 5 temporal bones. Extensive destruction in the wall of the bony external auditory canal and osteomyelitic destruction of the wall of the fallopian canal in the descending portion of the facial nerve was seen. The infection spread

beneath the otic capsule to erode the wall of the carotid canal and then extended into the central skull base.

Staging

Levenson et al, Corey et al, Benecke, and Davis et al have proposed staging systems for malignant external otitis (MEO).7,8,9 o These staging systems are generally based on extent of soft tissue/bony involvement

or development of neurologic complications. None of these staging systems has been widely adopted

Treatment
Medical Care
Treatment includes meticulous glucose control, aural toilet, systemic and ototopic antimicrobial therapy, and hyperbaric oxygen therapy.10

Systemic antibiotic choice: Until the development of third-generation antipseudomonal cephalosporins, long-term intravenous antibiotics using an antipseudomonal penicillin and aminoglycoside were the mainstay of medical treatment. o Several authors have demonstrated the effectiveness of intravenous ceftazidime

monotherapy in the treatment of malignant external otitis (MEO). Fluoroquinolones that attain high soft tissue and bone levels with oral doses were then developed. Subsequently, several authors have demonstrated the efficacy of oral ciprofloxacin monotherapy. Although no established treatment guidelines are available, case series and anecdotal experience suggest that initial outpatient therapy with oral ciprofloxacin is efficacious for patients without a fluoroquinolone allergy, cranial neuropathy, or intracranial complication and who do not require hospital admission for diabetes or pain management. The widespread use of fluoroquinolones for upper respiratory infections and simpler

ear infections is beginning to confound the typical clinical spectrum of malignant external otitis (MEO). Ciprofloxacin-resistant P aeruginosa has been increasingly isolated in patients with malignant external otitis (MEO), accounting for as many as 33% of isolates in patients who failed outpatient management in a study by Berenholz et al.11 Most notably in this patient population, 63% of isolates from 1998-2001 were resistant to ciprofloxacin, whereas only 15% of isolates were found to be resistant in the 10 years before this 3-year period. No increased morbidity or mortality was found in patients with ciprofloxacin-resistant Pseudomonas. Patients with resistant P aeruginosa require parenteral antibiotics with antipseudomonal beta-lactam antibiotics with or without an aminoglycoside. Duration of therapy o Symptoms and examination findings improve with appropriate therapy, but these changes do not correlate with the length of needed therapy. Despite symptom relief, prolonged antimicrobial treatment as indicated for osteomyelitis is still indicated. Imaging studies are helpful in determining the adequate length of treatment for each patient.

Treatment response should be evaluated with a gallium citrate Ga 67 scan every 4-6

weeks during treatment. Benecke recommended ending treatment 1 week after the gallium citrate Ga 67 scan findings return to normal and confirming this with a repeat scan 1 month after the treatment is stopped. Using this protocol for 13 patients, the average duration of treatment was 8.8 weeks with a range of 4-17 weeks. Hyperbaric oxygen therapy o This should be used only as an adjunct to antimicrobial therapy; it should not be used

alone. Hyperbaric oxygen therapy may be helpful for patients with complications, experiencing a poor response to therapy, or with recurrent cases.

Surgical Care

Chandler advocated surgery in his original report when appropriate antimicrobials were not available; he had very poor results, with a 50% mortality rate. Surgical removal of the lesion requires resection of large portions of the temporal bone. Because of the histopathology of malignant external otitis (MEO), removal of contiguous areas of bone may not be sufficient because of the spread of infection through vascular and fascial planes. Surgery is now reserved for local debridement, removal of bony sequestrum, or abscess drainage. Facial nerve decompression is not indicated for patients with facial paralysis.

Consultations

Consultation with internal medicine specialists is required for the management of diabetes and other comorbidities. Infectious-disease consultants may help with the choice of antibiotics in complicated cases.

Medication
The goals of pharmacotherapy are to reduce morbidity and prevent complications.

Antibiotics
The choice of antimicrobial therapy and whether treatment can be delivered PO versus IV, as monotherapy, or on an outpatient basis need to be carefully individualized to each patient. Refer to Medical Care for further discussion of these issues.

Ciprofloxacin (Cipro)

A DNA gyrase inhibitor that prevents DNA replication.

Adult

Dosing Interactions Contraindications Precautions

1500-2250 mg/d PO/IV divided bid/tid

Pediatric

<18 years: Not recommended >18 years: Administer as in adults

Dosing Interactions Contraindications Precautions Dosing Interactions Contraindications Precautions Dosing Interactions Contraindications Precautions

Ceftazidime (Fortaz, Tazicef, Tazidime)

Third-generation cephalosporin that inhibits bacterial cell wall synthesis by adhering to penicillinbinding proteins. Can be either bactericidal or bacteriostatic depending on the organism, tissue penetration, and drug dosage.

Adult

Dosing Interactions Contraindications Precautions

1-2 g IV q8h
Pediatric

Not established

Dosing Interactions Contraindications Precautions Dosing Interactions Contraindications Precautions Dosing Interactions Contraindications Precautions

Ticarcillin/clavulanate (Timentin)

Extended-spectrum penicillin/beta-lactamase inhibitor. Ticarcillin binds to penicillin-binding proteins, thus inhibiting bacterial cell wall synthesis. Clavulanate binds irreversibly to beta-lactamases, thus preventing inactivation of ticarcillin.

Adult

Dosing Interactions Contraindications Precautions

3.1 g IV q6h
Pediatric

Not established

Dosing Interactions Contraindications Precautions Dosing Interactions Contraindications Precautions Dosing Interactions Contraindications Precautions

Gentamicin (Garamycin, Jenamicin)

Binds to 30S ribosomal subunit, thus inhibiting bacterial protein synthesis. Aminoglycosides have bactericidal activity against P aeruginosa. Bacterial strains resistant to one aminoglycoside still may be sensitive to other antibiotics within this category.

Adult

Dosing Interactions Contraindications Precautions

3-5 mg/kg/d IV in equally divided doses q8h or 5-7 mg/kg/d IV administered qd; dose is adjusted based on serum drug levels
Pediatric

Not established

Dosing Interactions

Follow-up
Prognosis

Disease recurrence o Disease recurrence is reported in 9-27% of patients. o It usually is related to inadequate length of therapy and manifests as recurrent

Contraindications Precautions Dosing Interactions Contraindications Precautions Dosing Interactions Contraindications Precautions

o o
Mortality

headaches and otalgia, not as otorrhea. The ESR begins increasing again. Malignant external otitis (MEO) can recur as long as one year after treatment is completed; thus, a patient should not be considered cured until that time.

o o o

Chandler reported a mortality rate of 50% in the original series. The mortality rate has decreased to 20% with the introduction of appropriate antibiotics, improved imaging modalities, and increased awareness of the disease. Most current studies report a mortality rate of less than 10%, but mortality remains high for patients with cranial neuropathies (other than VII), intracranial complications, or with irreversible systemic immunosuppression.

Miscellaneous
Medicolegal Pitfalls

Failure to exclude a malignant neoplastic process Delays in diagnosis

Special Concerns

Infants and children o In 1988, Rubin et al reported malignant external otitis (MEO) in 15 children. Most did not have diabetes, and the more common predisposing risk factor was immune dysfunction.12 The facial nerve was affected more frequently than in adults, and other cranial neuropathies were not found. This is likely related to the underdeveloped mastoid process and the more medial location of the fissures of Santorini in children. Tympanic membrane involvement was common, and bacteremia was more common than in adults. Long-term morbidity was uncommon.

Fluoroquinolones are not approved by the Food and Drug Administration (FDA) for

use in the management of malignant external otitis (MEO) in the pediatric population, but they have been used widely and safely in the management of cystic fibrosis in children. Possible impact of managed care and delayed diagnosis because of late referrals: Insufficient duration of therapy by primary care physicians treating malignant external otitis (MEO) as an uncomplicated otitis externa may lead to emergence of drug resistance.

Multimedia
Media file 1: Anatomy of the ear.

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