Skull base osteomyelitis is a rare complication of otitis externa in which soft tissue pathogens have spread to the periosteum and temporal bone of the skull causing necrosis.

1. Malignant Otitis Externa
Dr. Amro Yousef Alamleh

2. Malignant Otitis Externa
 Skull base osteomyelitis is a rare complication of otitis externa  soft tissue
pathogens have spread to the periosteum and temporal bone of the skull
causing necrosis.
 This may be associated with involvement of the facial nerve, carotid artery and
jugular vein, including the bulbar and hypoglossal nerves.
 The infection may then progress to other bones of the skull base.

3. Epidemiology
 Skull base osteomyelitis most frequently affects the elderly and diabetic
 Patients are usually older than 60 years of age
 There is a male preponderance with a ratio of 2 : 1.12.
 Various factors are said to account for the susceptibility of elderly diabetics to
skull base osteomyelitis including :-
1. Innate defects in humoral immunity
 Weakened immune response to Pseudomonas aeruginosa infection
 Poor phagocytosis of polymorphonuclear leucocytes.
2. High pH of their cerumen.
3. Endarteritis, microangiopathy and small vessel obliteration

4. Predisposing Factors
 Conditions causing immunosuppression are also predisposing factors to skull
base osteomyelitis such as
 HIV/AIDS
 Steroid usage
 Chemotherapy
 Anaemia
 Leukaemia
 Lymphoma
 Neoplasia
 Renal transplantation

5.  HIV-affected patients with skull base osteomyelitis tend to be
 Younger than those with diabetes
 More likely to have a fungal infection (i.e. Aspergillus sp.), particularly
when CD4 counts are less than 50 cells / mm.
 Aspergillus fumigatus, is the most common fungal organism isolated. It is
associated with a worse prognosis than Pseudomonas when it is the
causative agent

6. Diagnosis
 The diagnosis of skull base osteomyelitis is based on
 History + Clinical features
 Microbiology for culture
 Radiological changes within the bone of the skull base
 Histology showing inflammation without neoplasia
 Fungal pathogens may also be identified on silver staining of histological
sections.

7. Clinical Features
 Patients with skull base osteomyelitis are usually elderly diabetics.
 There is usually a history of ear canal trauma.
 Otalgia that is nocturnal, deep, lancinating and disproportionate to the clinical
signs is highly suggestive of osteomyelitis. It is often resistant to analgesics. It
is the most common presenting symptom with a prevalence of 75–100%.
 Purulent otorrhoea, the second most common symptom and sign.
 Inspection of the floor of the ear canal may reveal granulation tissue or
exposed bone.
 The granulations should be sent for histological analysis to exclude
malignancy, histiocytosis and tuberculosis.
 Patients with HIV infection often lack granulation tissue.
 There may also be a polyp or granuloma in the canal obstructing the view of
the TM.

8.  The HL is usually conductive due to EAC obstruction by granulation or
oedema.
 SNHL is usually due to pre-existing presbycusis.
 As bony destruction and inflammation progresses medially through the skull
base to the foramina, cranial neuropathies ensue initially with facial paralysis
(in up to 25% of patients). This is followed by cranial nerves IX, X, XI, XII
and then VI and II.
 Meningitis, cerebral abscess and sigmoid sinus thrombosis are late signs that
are associated with a poor prognosis.
 Children with skull base osteomyelitis usually develop facial nerve palsies
earlier due to their more medial fissures of Santorini and their underdeveloped
mastoid process.
 Parotitis and trismus due to masseter myositis and TMJ involvement is a rare
clinical feature that has been described.

9. Levenson’s criteria
 Levenson’s criteria for diagnosing MOE includes:
1. Refractory otitis externa  not respond to adequate treatment for 2-3
weeks
2. Severe nocturnal otalgia
3. Purulent otorrhoea
4. Granulation tissue in the EAC
5. Growth of Pseudomonas aeruginosa from the EAC
6. The presence of diabetes or immune-compromised state
7. Positive Bone scan

10. Staging
 Clinico-pathological classification system has divided the disease process into 4
stages.
 Stage 1: Clinical evidence of malignant O.E with infection of soft tissues beyond
the EAC, but negative Tc-99 bone scan.
 Stage 2: Soft tissue infection extending beyond the EAC with a positive Tc-99
bone scan.
 Stage 3: As above, but with cranial nerve paralysis
 Stage 3a: Single cranial nerve palsy.
 Stage 3b: Multiple cranial nerve palsy.
 Stage 4: Meningitis, empyema, sinus thrombosis or brain abscess.

11. Microbiology
 Pseudomonas aeruginosa, a Gram-negative obligate aerobe, is the most common
bacteria species in skull base osteomyelitis.
 It has the ability to invade local vasculature and cause a focal coagulative
necrosis of the surrounding tissue.
 Virulent species have a mucoid surface layer that confers protection against
phagocytosis.
 They may produce lytic enzymes (for example, collagenases and elastases)
and endotoxins, resulting in a necrotizing vasculitis.
 Some strains also produce neurotoxins, which likely play a role in the
development of cranial neuropathies.

12.  Staphylococcus aureus, Staphylococcus epidermidis, Proteus mirabilis,
Klebsiella oxytoca, Klebsiella pneumonia, Burkholderia cenocepacia,
Enterobacter cloacae and Streptococcus constellatus are other bacteria that
have been implicated in the pathogenesis of skull base osteomyelitis.
 Fungal infections are more commonly associated with the
immunocompromised (e.g. HIV/AIDS) than with diabetics.
 Aspergillus fumigatus, is the most common fungal organism isolated. It is
associated with a worse prognosis than Pseudomonas when it is the
causative agent.
 Others include Aspergillus niger, Aspergillus flavus, Candida sp., Malassezia
sympodialis and Scedosporium apiospermum.

13. Labs
 WBC count can be normal or slightly elevated.
 Inflammatory markers (ESR and CRP) are usually high and can be used as an
indicator for the response for antimicrobial therapy. Once the disease has
been identified, levels of ESR and CRP should be checked and followed
regularly until they are back in the normal range. ESR starts to decrease within
two weeks of starting treatment.
 Blood glucose should be checked in patients with diabetes to assess their
baseline, as MOE can affect the baseline glucose intolerance.
 Non-diabetic patients should be evaluated for diabetes or other
immunocompromised conditions.
 Culture and sensitivities from the EAC Cultures from the ear drainage are
to be done before initiating antimicrobial treatment.
 Biopsy of the EAC should be obtained to exclude other causes, such as
malignancy or cholesteatoma.

14. Imaging
 A high-resolution CT-scan is valuable in diagnosing bony erosion and reduced
density in the skull base. However, the value of CT scans is limited due to it
only detecting bony demineralization of 30% or greater.
 MRI is superior to CT with detecting anatomical locations and invasion of
soft-tissue components. MRI is also better in evaluating intracranial
complications such as thrombosis and intracranial spread.
 However, it is hard to differentiate between active inflammation and resolving
infection  the use of CT and MRI imaging does not correlate to the
prognosis and outcome of the disease.

15. Nuclear studies
 Nuclear imaging is useful in diagnosing skull base osteomyelitis, defining its
extent and evaluating response to treatment and resolution of infection.
 Technetium-Tc 99m-methylene-diphosphonate (99mTc- MDP) or Technetium-
Tc 99-hydroxymethylene-diphosphonate (99mTc-MDP) scintigraphy has
almost 100% sensitivity. Its radiotracer accumulates in areas of high
osteoblastic activity even in early cases of the disease.
 It is useful for the initial evaluation of the disease, but the test is not useful in
assessing the prognosis of the disease, as it stays positive for a long period,
even after the resolution of the infection.

16.  Gallium-67-citrate scanning is often utilized to monitor treatment response.
It is based on the propensity of Gallium Ga 67 citrate to accumulate in areas of
active inflammation in both soft tissue and bone. The affected area usually
shows increased uptake.
 It should ideally be repeated every 4 weeks to monitor response to antibiotics
until it is no longer positive.
 Nuclear studies are not sufficient to show the anatomical extent of the disease.

17. Treatment
 Aural Toilet.
 Control of Diabetes.
 Patients with poorly controlled diabetes are more susceptible to developing skull
base osteomyelitis than diabetics with satisfactory control of serum glucose levels.
 Aggressive glycaemic control in diabetic patients can be as crucial a
management strategy as systemic antimicrobial therapy. Achieving good control of
serum glucose may be difficult with invasive infection.

18. Systemic Antibiotics
 Long-term systemic culture-directed antimicrobial therapy is the mainstay of
treatment of skull base osteomyelitis.
 The duration of treatment depends on the response to therapy, which is
evaluated using a gallium citrate Ga 67 scan every 4 to 6 weeks during
treatment.
 The treatment should be stopped one week after a normal gallium citrate Ga 67
scan.

19. Antibiotics against P. aeruginosa
1. Antipseudomonal penicillins:
 Carboxypenicillins (carbenicillin and ticarcillin)
 Ureidopenicillins (mezlocillin, azlocillin, and piperacillin).
2. Cephalosporins
 Ceftazidime, Cefepime, Cefoperazone, cefpirome, ceftobiprole,
 but not cefuroxime, cefotaxime, or ceftriaxone
3. Aminoglycosides
 Gentamicin, Amikacin, Tobramycin
 but not kanamycin
4. Quinolones
 Ciprofloxacin, Levofloxacin
 but not moxifloxacin
5. Carbapenems
 Meropenem, Imipenem, doripenem,
 but not ertapenem
6. Monobactams (aztreonam)
7. Polymyxins (polymyxin B and colistin)

20.  Fluoroquinolones are antipseudomonal, have good bone penetration and good oral
bioavailability, and have fewer side effects.
 Monotherapy with oral ciprofloxacin (750 mg twice daily) is the preferred initial
regimen.
 Some experts still advocate parenteral antimicrobials converted to oral once the serum
CRP and ESR start to decline.
 The addition of rifampicin (600 mg twice daily) has also been suggested, again with no
direct evidence that it confers additional benefit.
 The incidence of Pseudomonal resistance to fluoroquinolones worldwide is increasing.
alternatives in the context of resistance.
 Cephalosporins active for pyocyanin (i.e. ceftazidime, cefepime),
 Penicillins (i.e. ticarcillin, clavulanate)
 Aminoglycosides
 Amphotericin B is the antifungal agent of choice for skull base osteomyelitis of fungal
origin. Oral itraconazole may be used after a successful course of amphotericin B.

21. Hyperbaric Oxygen
 The use of hyperbaric oxygen as an adjunct to systemic antimicrobial therapy
 It increases the partial pressure of oxygen, relieving hypoxia
 It enhancing the oxidative killing of microbes.

22. Surgery
 It is primarily performed
 To obtain specimens for culture, to locally debride granulation tissue and to
exclude malignancy.
 To remove dead sequestra and drain associated abscesses.
 Facial nerve decompression for complete facial palsies has unproven
therapeutic benefit.

23. Prognosis
 The poorer prognosis was seen in patients who experienced any of the
following:
 Cranial neuropathies
 Extensive granulations in external auditory canal
 Bilateral symptoms
 Positive aspergillus cultures.
 Elderly patients had a higher chance of developing complications and had a
higher mortality rate.

24. Recurrence
 The recurrence rate of MOE is high, reaching 15% to 20% when ESR starts to
rise again.
 MOE can recur up to one year after treatment; therefore, the patient should
be followed up regularly for one year before being considered cured.
 Mortality
 With the advanced treatment modalities, the mortality rate dropped from a high
of 50% in the past to 10% to 20%.