| Disclaimer: The information contained within the Grand Rounds Archive is intended for use by doctors and other health care professionals. These documents were prepared by resident physicians for presentation and discussion at a conference held at Baylor College of Medicine in Houston, Texas. No guarantees are made with respect to accuracy or timeliness of this material. This material should not be used as a basis for treatment decisions, and is not a substitute for professional consultation and/or peer-reviewed medical literature. Skull Base Osteomyelitis Brief history of skull-based osteomyelitis: The disease process was first cited by Toulmouche in 1883. In 1959, Meltzer and Kelemen were the first to describe Pseudomonas chondritis and osteomyelitis of the external auditory canal and temporal bone. In 1968, Chandler coined the term “malignant otitis externa” due to the high mortality of the disease and recommended surgical debridement of all infection with systemic antibiotics as adjuvant treatment at that time. The nomenclature regarding skull-based osteomyelitis can be confusing. Necrotizing external otitis generally refers to a soft tissue infection surrounding the external auditory canal without any bony involvement. Malignant otitis externa refers to an infection involving both the external auditory canal and the surrounding bone. Given the fact that it is not a neoplastic process, malignant otitis externa has been replaced by the term skull-based osteomyelitis in most of the literature. Both malignant otitis externa and skull-based osteomyelitis are used interchangeably in the literature. The external auditory canal permits sound transmission as well as protects middle and inner ears from trauma, infection, and environmental extremes. It is the only skin- lined cul-de-sac in the human body with a keratinizing stratified squamous epithelium. It comes from the first branchial cleft and is completely canalized by the seventh gestational month. The shape of the external auditory canal in the neonate is nearly straight and by age nine, it has nearly achieved its adult size and characteristic S-shape. The canal is divided into an outer cartilaginous one-third and inner bony two-thirds with the narrowest portion at this junction. The EAC cartilage is attached medially to the bone canal wall with dense connective tissue. Anteroinferiorly are two horizontal fissures in the cartilaginous canal called the fissures of Santorini. These fissures allow for increased flexibility of the cartilaginous canal, but also serve as a pathway for spread of neoplasm or infection to surrounding tissues. This slide demonstrates the two fissures of Santorini as well as the squamous part and the tympanic part of the temporal bone where surrounding infection may spread. Skull-based osteomyelitis originates from a chronic infection, which has been inadequately treated. It is a true infection of the bone and this talk today will focus primarily on skull-based osteomyelitis originating from otitis externa, which has been inadequately treated. It is important to note, however, that this infection can come from anywhere including chronic otitis media, sphenoid sinusitis, or any inadequately treated infection near the skull base. On presentation, the external auditory canal is usually ulcerated and granulation tissue typically forms at the level of the epithelium. This is a key step in the pathophysiology because it breaks down the normal skin barrier from infection. Acute and chronic inflammation then surrounds this area and penetrates the dermis to gain access to the osseous external auditory canal and skull base through the previously described fissures of Santorini. Patterns of infectious spread: The infection may spread anteriorly to involve the parotid gland, temporomandibular joint, or cranial nerve VII at the exit of the stylomastoid foramen. It may also spread posteriorly to the mastoid and vertical portion of cranial nerve VII or inferomedially to the skull base including the carotid artery, the jugular bulb, and the sigmoid sinus. Infection typically spreads through the Halversian system of compact bone with progressive replacement of compact bone with granulation tissue. Bone destruction is both osteoplastic and osteoclastic. Multiple abscess formations may occur and involvement of pneumatized trabeculated bone usually occurs late. Facial nerve paralysis results typically when the extra-temporal segment becomes surrounded by infection at the styloid and mastoid foramen. Cranial nerves IX, X, or XI palsies can occur when the jugular foramen becomes involved. This schematic diagrams the basic pathophysiology, which is true for skull-based osteomyelitis originating in the external auditory canal or really can be reflected upon any osteomyelitis. You have a chronic infection, which is inadequately treated leading to a cellulitis, a chondritis, an osteitis, and finally osteomyelitis. From a histopathological standpoint, the histopathology shows a necrotizing inflammation with granulation tissue and acute and chronic inflammatory cell infiltrate extending to the bone. Here is the acute and chronic infiltrate. There is a thick acellular collagen that replaces most of the previous lying tissue, as seen here. The squamous epithelium is typically ulcerated and hyperplastic. The external auditory canal provides ideal conditions for growth of microorganisms because of its warmth, darkness, moisture, and presence of debris. Pseudomonas aeruginosa is a common pathogen cultured in skull-based osteomyelitis originating from the external auditory canal. It is a gram negative, motile, aerobic rod, which produces a protective polysaccharide layer that prevents phagocytosis and antibiotic penetration. It is typically only a pathogen when defense mechanisms are impaired and it is not normally cultured from the external auditory canal, but will colonize when a moist environment is present. Aspergillus has also been reported as a responsible pathogen for skull-based osteomyelitis in the immunocompromised patient. It typically begins in the middle ear or mastoid as opposed to the external auditory canal. Staph aureus, Staph epidermidis, Proteus, and Salmonella have all been reported as etiologic agents of skull-based osteo originating from the external auditory canal. Most cases of skull-based osteo occur in elderly diabetic patients. This is based on two theories. One is their susceptibility to microangiopathic changes facilitating tissue necrosis and reducing antibiotic uptake. The second is their altered immune response compromised by poor migration, reduced chemotaxis, and defective vagocytosis of polymorphonuclear leukocytes. Driscoll et al in 1993 showed that the cerumen from diabetic ears had a higher average pH as compared to the nondiabetic population and he postulated that the alkaline pH could provide a beneficial environment for bacterial overgrowth. The increased incident of AIDS has also been associated with an increase in skull-based osteomyelitis, but the majority of cases are secondary to Pseudomonas, but they are also reports of Aspergillus as well, and the mechanism is again thought to be an altered cell-mediated immunity. Skull-based osteomyelitis has also been reported in diabetic and immunosuppressed children. These patients are typically more severely ill at initial presentation and cranial nerve VII involvement is more common, likely due to its lateral location and the underdeveloped mastoid placing it closer to the vulnerable bony cartilage in this junction. On clinical presentation, a high index of suspicion for skull-based osteo should be maintained in any diabetic patient presenting with external otitis refractory to a standard course of antibiotic therapy. Characteristic clinical symptoms include otalgia of long duration and out of proportion for routine external otitis, diurnal headaches centered over the temporal and parietal regions, otorrhea, hearing impairment, or fullness in the ear. The most important clinical indicator on examination is granulation tissue in the floor of the external auditory canal at the bony cartilage in this junction. Edema of soft tissue surrounding the canal and associated perioral lymphadenopathy may also be present. In more severe cases, patients will complain of trismus, cranial nerve involvement, or signs and symptoms of sigmoid sinus thrombosis. This slide demonstrates an exam of the external auditory canal showing a bloody discharge in the floor of the canal as well as granulation tissue at the bony cartilaginous junction. Differential diagnosis for skull-based osteonmyelitis includes necrotizing otitis externa, carcinoma, herpes zoster oticus, Paget’s disease, nasopharyngeal malignancies, metastatic lesions of the clivus, or fibrous dysplasia. On diagnosing skull-based osteomyelitis, history and physical must first be performed and the patient should have clinical symptoms previously described. The white blood cell count is usually normal and there is little or no fever. The sed rate is usually markedly elevated and the biopsy of granulation tissue needs to be negative for carcinoma. Radiologic tests are required for the diagnosis of skull-based osteomyelitis to confirm bony involvement. Modalities used for this include CT, MRI, technetium bone scans, gallium scans, and indium 1-11 labeled leukocyte scans. CT defines the location and the extent of the disease at initial evaluation. It is definitive in determining osteitis when positive for bony destruction, but scans will only show abnormalities when demineralization of 30% or more occurs. Once demineralization occurs, a CT scan rarely returns normal and thus is not a reliable modality in assessing response to therapy. This slide demonstrates just some bony destruction of the external auditory canal as seen in skull-based osteomyelitis originating from the EAC. MRI is complimentary to CT in determining soft tissue changes associated with skull-based osteomyelitis. It is helpful in the initial evaluation of skull-based osteomyelitis to determine the full anatomical extent of soft tissue disease. One of its pertinent positives is that it is available for immediate interpretation where most nuclear medicine scans take several days for results to return. One negative is that is does not show any bony involvement and thus ineffective as a single modality for skull-based osteomyelitis. A positive technetium scan is indicative of skull-based osteomyelitis or any osteomyelitis for that matter. Technetium is absorbed by osteocytes and osteoblasts and is associated with osteogenic activity. This activity can come from infection, neoplasm, or traumatic bone repair. This test does not depend on demineralization of bone and it may remain positive for several months to years after the osteomyelitis has resolved. Gallium scans are also very effective. Gallium is absorbed by macrophages and reticular endothelial cells over 48-72 hours. They are a sensitive indicator of infection, which quickly returns to normal after an infection has clearedStokkel et al in 1997 proposed a lesion and non-lesion ratio of 1 +/- .1 during follow up as highly indicative of recovery. Weber et al in 1995 compared the results of simultaneously acquired indium and technetium scan bone spec scans versus CT scan in 20 patients with confirmed skull-based osteomyelitis. He found that the combined indium technetium scan specs were superior to CT scan in the evaluation of the skull-based osteomyelitis. He suggested that the indium technetium specs were the best modality to monitor progression of disease, but in his study he did not obtain gallium scans or compare his results to gallium scans. Benecke in 1989 proposed the following staging system for skull-based osteo originating from the external auditory canal: Stage I disease has a positive gallium scan and a negative technetium scan and the extent of the disease is only to the soft tissue, which we have defined as a necrotizing otitis externa. Stage II is a true osteomyelitis with a positive gallium and technetium scan, but the disease is limited to the mastoid. Stage III disease is also true osteomyelitis and it has a positive gallium and technetium scan and is defined as extensive skull-based osteomyelitis. He further went on to state that the stage III disease could spread in three distinct patterns, posteriorly to involve the occipital bone, anteriorly to involve the facial bones, or medially across the clivus to involve the contralateral temporal bone. Treatment for skull-based osteomyelitis has evolved from the initial radical surgical approach described by Chandler in 1968 to the present form of long-term antibiotics specific for culture sensitivities. Patients with skull-based osteomyelitis often suffer from multiple medical problems associated with poorly controlled diabetes mellitus, in particular renal dysfunction. Patients must be carefully monitored for strict blood glucose control. It is well accepted in the literature that daily debridement of the external auditory canal is performed until any granulation tissue resolves. Use of topical antimicrobial agents is controversial because these drops will affect future culture results if there is not a response to therapy. Once the diagnosis of skull-based osteomyelitis has been confirmed, long term antimicrobial therapy remains the mainstay of treatment with three general protocols; and aminoglycoside and a β-Lactamase antibiotic, a third generation cephalosporin, Ceftazidime, or an oral quinolone ciprofloxacin. Anti-pseudomonal penicillins are bacteriocidal and work synergistically with aminoglycosides against Pseudomonas. They are given intravenously. They are dual therapy, which helps prevent resistance, but the penicillin may inactivate the aminoglycoside when given simultaneously and thus they must be given at separate times. Aminoglycosides are also bacteriocidal and the known complications including ototoxicity and nephrotoxicity. Pedersen et al in 1997 recently reported a series of 22 patients treated with a recurrence rate of 14% and an eventual cure rate of 95% on this regimen. The majority of these patients had stage II disease. Ceftazidime is a third generation β-Lactamase cephalosporin with good activity against Pseudomonas. It is bacteriocidal causing bacterial cell lysis. It is administered intravenously t.i.d. and it provides good penetration into the CSF. Kimmelman in 1989 reported successful treatment in seven of eight patients with an eventual cure rate of 100% and no drug induced complications with this regimen. Ciprofloxacin is an oral quinolone, which has significant in vitro activity against Pseudomonas. It effectively penetrates the bone and is well absorbed from the GI tract. It works by inhibiting bacterial DNA gyrase. The largest series using ciprofloxacin was reported by Lang in 1989 with successful treatment of 21 of 23 patients with minimal side effects and early home therapy. Resistant rates have been reported of up to 20% for this regimen. Surgical intervention for skull-based osteo is reserved for those individuals not responding to antibiotic therapy. When necessary, limited debridement of all involved tissues is often performed. Furthermore, surgery may be required for appropriate tissue diagnosis, culture and sensitivity. Hyperbaric oxygen has been used as an adjuvant therapy for refractory cases of skull-based osteomyelitis. It is usually well tolerated. It works by increasing the oxygen partial pressure and oxygen tension, which aids the PMNs ability to kill aerobic pathogens and promotes neomicroangiogenesis. Davis et al in 1992 reported success in 16 patients treated with hyperbaric oxygen in addition to the antibiotic therapy. Fungal skull-based osteomyelitis arises most commonly in patients with end stage AIDS and hematologic malignancies. Aspergillus species fungi were the pathological organism in 22 of the 24 reported cases of skull-based osteomyelitis in the literature. An important distinguishing characteristic is that granulation typically is not a common finding on physical exam. This is thought to be to the diminished immune response of these patients. The infectious process often starts in the mastoid air cells or middle ear space. Surgical debridement and an Amphotericin β are the current mainstays of treatment and the resolution of an infection greatly depends on the patient’s overall health and the severity of their underlying disease. In summary, in diagnosing skull-based osteomyelitis originating from the external auditory canal, required modalities of radiological modalities includes CT scan demonstrating bony destruction with MRI to evaluate soft tissue involvement. If the CT scan is not definitive for bony destruction, then a positive technetium bone scan is necessary. Suggestive factors include granulation tissue in the floor of the external auditory canal negative for malignancy, an elevated sed rate, positive Pseudomonas cultures, a patient with diabetes or in an immunocompromised state, or severe otalgia with headache. Definitive care for skull-based osteomyelitis has evolved to the present protocol of long term antibiotic therapy with regular meticulous cleaning of the external auditory canal. Appropriate antibiotic therapy is started as soon as cultures and sensitivities are available. Response to therapy is monitored by gallium or indium scan, and the duration of treatment is determined by clearing on the gallium or indium scans and clinical response, not by a predetermined arbitrarily selected time period. Surgical intervention is reserved for unresponsive patients. In conclusion, aggressive medical therapy is warranted to prevent morbidity and mortality associated with skull-based osteomyelitis. Outcomes are now improved because of a better understanding of skull-based osteomyelitis pathophysiology, improved diagnostic tests, and more effective antibiotic therapy. Given the present treatment protocols, survival has improved from 23% as reported in the last 1960’s to greater than 90% over the last 30 years. Case Presentation: WC is a 51-year-old white male with a past medical history significant for insulin-dependent diabetes mellitus who presented to the VAMC emergency department with complaints of pain and discharge from his right ear. An Otolaryngology consult was obtained to rule out a “severe otitis externa.” Upon further questioning, the patient denied any previous otology problems or surgery. He denied any trauma to the ear, vertigo, headache or diplopia. He has no other significant past medical history except for his DM with fair control. On physical examination, the patient was afebrile with a normal white blood count and blood glucose level of 206. There was no mastoid or auricular tenderness. The right EAC was inflamed with minimal purulence and a small excoriation in the floor. The TM was inflamed with no visible perforation. Weber localized to the right. Cranial nerves II-XII were intact bilaterally. Patient was started on a PO course of Ceftin and Cortisporin Otic drops for two weeks. He was followed in the Otolaryngology Clinic as an outpatient with complete resolution of symptoms. Follow-up at three weeks was consistent with a normal exam after removal of EAC debris. Follow-up audiogram was essentially normal. Bibliography: Al-Shihabi BA. Carcinoma of temporal bone presenting as malignant otitis externa. J Laryngol Otol 1992.106:908-910. Babiatzki A, Sade J. Malignant external otitis. J Laryngol Otol 1987;101:205-210. Bailey BJ. Head & Neck Surgery-Otolaryngology, 2 nd Edition. Philadelphia: Lippincott-Raven, 1998. Bath AP, Rowe JR, Innes AJ. Malignant otitis externa with optic neuritis. J Laryngol Otol 1998;112:274-277. Behjati K, Boyd CM, Balachandran S, Pallin C. Value of gallium-67 SPECT in a patient with “malignant” otitis externa. Clin Nucl Med 1987;12:229-230. Benecke JE Jr. Management of osteomyelitis of the skull base. Laryngoscope 1989;99:1220-1223. Chandler JR. Malignant external otitis. Laryngoscope 1968;78:1257-1294. Chandler JR, Grobman L, Quencer R, Serafini A. Osteomyelitis of the base of the skull. Laryngoscope 1986;96:245-251. Clark WB, Brook I, Bianki D, Thompson DH. Microbiology of otitis externa. Otolaryngol Head Neck Surg 1997;116:23-25. Cohen D, Friedman P. The diagnostic criteria of malignant external otitis. J Laryngol Otol 1987;101:216-221. Cohen D, Friedman P, Eilon A. Malignant external otitis versus acute external otitis. J Laryngol Otol 1987;101:211-215. Davis JC, Gates GA, Lerner C, Davis MG Jr, Mader JT, Dinesman A. Adjuvant hyperbaric oxygen in malignant external otitis. Arch Otolaryngol Head Neck Surg 1992;118:89-93. Driscoll PV, Ramachandrula A, Drezner DA, Hicks TA, Schaffer SR. Characteristics of cerumen in diabetic patients: A key to understanding malignant external otitis? Otolaryngol Head Neck Surg 1993;109:676-679. Gherini SG, Brackmann DE, Bradley WG. Magnetic resonance imaging and computerized tomography in malignant external otitis. Laryngoscope 1986;96:542-548. Gilbert DN, Tice AD, Marsh PK, Craven PC, Preheim LC. Oral ciprofloxacin therapy for chronic contiguous osteomyelitis caused by aerogic gram-negative bacilli. Am J Med 1987;82(Suppl 4A):254-261. Grobman LR, Ganz W, Casiano R, Goldberg S. Atypical osteomyelitis of the skull base. Laryngoscope 1989;99:671-676. Hern JD, Almeyda J, Thomas DM, Main J, Patel KS. Malignant otitis externa in HIV and AIDS. J Laryngol Otol 1996;110:770-775. Kimmelman CP, Lucente FE. Use of Ceftazidime for malignant external otitis. Am Otol Rhinol Laryngol 1989;98:721-725. Kraus DH, Rhem SJ, Kinney SE. The evolving treatment of necrotizing external otitis. Laryngoscope 1988;98:934-939. Lang R, Goshen S, Kitzes-Cohen R, Sade J. Successful treatment of malignant external otitis with oral ciprofloxacin: Report of experience with 23 patients. J Infect Dis 1990;161:537-540. Levenson MJ, Parisier SC, Dolitsky J, Bindra G. Ciprofloxacin: Drug of choice in treatment of malignant external otitis (MEO). Laryngoscope 1991;101:821-824. Levin WJ, Shary JH III, Nichols LT, Lucent FE. Bone scanning in severe external otitis. Laryngoscope 1986;96:1193-1195. Meltzer PE , Lelemen G. Pyocyaneous osteomyelitis of the temporal bone, mandible and zygoma. Laryngoscope 1959;69:1300-1315. Midwinter KI, Gill KS, Spencer JA, Fraser ID. Osteomyelitis of the temporomandibular joint in patients with malignant otitis externa. J Laryngol Otol 1999;113:451-453. Nadol JB Jr. Histopathology of pseudomonas osteomyelitis of the temporal bone starting as malignant external otitis. Am J Otolaryngol 1980;1:359-371. Ostfeld E, Aviel A, Pelet D. Malignant external otitis: The diagnostic value of bone scintigraphy. Laryngoscope 1981;91:960-964. Pedersen HB, Rosborg J. Necrotizing external otitis: Aminoglycoside and ß-lactam antibiotic treatment combined with surgical treatment. Clin Otolaryngol 1997;22:271-274. Shupak A, Greenberg E, Hardoff R, Gordon C, Melamed Y, Meyer WS. Hyperbaric oxygenation for necrotizing (malignant) otitis externa. Arch Otolaryngol Head Neck Surg 1989;115:1470-1475. Stokkel PM, Takes RP, van Eck-Smit BLF, Baatenburg de Jong RJ. The value of quantitative gallium-67 single-photon emission tomography in the clinical management of malignant external otitis. Eur J Nucl Med 1997;24:1429-1432. Uri N, Gips S, Front A, Meyer SW, Hardoff R. Quantitative bone and 67 Ga scintigraphy in the differentiation of necrotizing external otitis from severe external otitis. Arch Otolaryngol Head Neck Surg 1991;117:623-626. Weber PC, Seabold JE, Graham SM, Hoffmann HH, Simonson TM, Thompson BH. Evaluation of temporal and facial osteomyelitis by simultaneous in-WBC/Tc-99m-MDP bone SPECT scintigraphy and computed tomography scan. Otolaryngol Head Neck Surg 1995;113:36-41. Wormald PJ. Surgical management of benign necrotizing otitis externa. J Laryngol Otol 1994;108:101-105. Yao M, Messner AH. Fungal malignant otitis externa due to Scedosporium apiospermum. Ann Otol Rhinol Laryngol 2001;110:377-380. Grand Rounds Archive | Department Home page BCM Public | BCM Intranet | Privacy Notices | Contact BCM | BCM Site Map | ©2001-2005 Baylor College of Medicine
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