- Email: [email protected]
Stratification for malignant external otitis
Otolaryngology–Head and Neck Surgery (2007) 137, 301-305
ORIGINAL RESEARCH
Stratification for malignant external otitis Uri Peleg, MD, Ronen Perez, MD, David Raveh, MD, Daniel Berelowitz, MD, and David Cohen, MD, Jerusalem, Israel OBJECTIVE: To propose a CT-based method for early identification of severe cases of malignant external otitis (MEO) by correlating between initial CT findings and clinical course. STUDY DESIGN AND SETTING: Eighteen MEO patients who underwent CT on admission were included in this retrospective study conducted at a tertiary center. The number and extent of anatomical areas involved according to CT were compared to clinical course severity. RESULTS: The patients were categorized into two groups according to clinical course. There were 13 patients in the “nonsevere” group and 5 in the “severe.” In six out of eight CT anatomical areas the “severe” group had significantly higher scores (P ⬍ 0.05 to P ⬍ 0.0005). The average number of areas involved in the “nonsevere” group was 2.9 and in the “severe” 5.4 (P ⬍ 0.0005). CONCLUSION: We found a clear correlation between clinical course and initial CT findings in MEO patients. Based on these findings it may be possible to predict clinical course severity according to initial CT. © 2007 American Academy of Otolaryngology–Head and Neck Surgery Foundation. All rights reserved.
T
he term “malignant external otitis” (MEO) was coined by Chandler in 1968 to describe a life-threatening infection of the ear and skull base.1 Since then, the knowledge of the disease on one hand, and the antibiotic treatment on the other, has improved markedly. Therefore, the diagnosis is usually made in the early stages and in many cases the course of disease is less dramatic.2,3 The common diagnostic criteria in most studies include severe otalgia which worsens at night, prolonged external otitis unresponsive to local treatment, external auditory canal granulations, pseudomonas aeruginosa in cultures, diabetes mellitus (DM) or other immune suppression, and a positive bone scan.4-8 MEO was divided by Benecke into necrotizing otitis externa (NOE), in which only soft tissues and cartilage are involved, and skull base osteomyelitis (SBO), in which temporal or skull base bones are involved.9 On the other hand, Slattery and Brackmann used the term SBO as a substitute for MEO.10 This classification is useful for determining the length of treatment.9 Further staging methods were offered using mainly clinical criteria (cranial nerves and intracranial involvement),4
while others used Gallium (Ga) and Technecium (Tc) scans for staging,9 or a combination of bone scan and clinical findings.8 During the nineties we treated five patients who required prolonged hospitalization and numerous extensive operations. It is their course of disease, as well as the CT findings on admission, which led to this study. Our aim was to offer a method by which MEO patients may be stratified to those with potentially severe disease and those with mild disease, by correlating the initial CT results with the clinical course of disease. “Severe disease,” according to our stratification, may be considered as one of the factors influencing the decision for early surgical intervention as an adjunct to antibiotic therapy.
PATIENTS AND METHODS Between the years 1990 and 2000, 18 patients diagnosed with MEO underwent CT and Tc scan on admission. Their medical files and imaging were retrospectively analyzed with the approval of the Institutional Review Board. All our MEO patients fulfilled the common diagnostic criteria mentioned above and were treated as inpatients. We were able to retrieve the CT and Tc scan results of all the patients, but Ga scans of only two patients. Tc and Ga scans were used to distinguish between patients with skull base osteomyelitis and those with soft-tissue inflammation. A high-resolution CT of the temporal bone followed by a CT with contrast media (for soft tissue areas) was obtained. MRI was performed only in five patients, when a more accurate delineation of soft tissue or evaluation of intracranial involvement was needed (usually to aid surgical considerations). We initiated antibiotic treatment immediately after obtaining cultures, with a combination of a fluoroquinolone (usually ciprofloxacin) and an anti-pseudomonal cephalosporin (usually ceftazidime). Local treatment included daily external canal suction and fluoroquinolone drops. Debridement of inflamed tissues was performed when needed. Prior to obtaining the results of the present study, more extensive surgery was reserved only for patients with nonrespon-
Received December 12, 2006; accepted February 20, 2007.
0194-5998/$32.00 © 2007 American Academy of Otolaryngology–Head and Neck Surgery Foundation. All rights reserved. doi:10.1016/j.otohns.2007.02.029
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Table 1 Scoring method of the CT findings by their severity at each area Severity score Area
0
1
2
3
External canal Mastoid Middle ear Nasopharynx Parotid Temporal bone* TMJ Skull base
NI NI NI NI NI NI NI NI
Mild thickening Mucosal thickening Mucosal thickening Mild asymmetry, ET open Mild swelling/infiltration Bone destruction Enlarged joint space Bone destruction
Moderate thickening Fluid & air Fluid & air Mild asymmetry, ET thickened/closed Severe swelling/infiltration – Bone destruction –
Passage closed Almost full Almost full Severe asymmetry – – – –
NI, no involvement; ET, Eustachian tube; TMJ, temporomandibular joint. *Temporal bone includes bony external canal and scutum.
sive extensive disease after 4 weeks of the above-mentioned medical treatment, for rapidly expanding disease, or when cranial nerve involvement appeared. Termination of inpatient treatment was determined mainly by clinical improvement and negative cultures, and aided by imaging (CT and bone scans). Seventeen out of the 18 patients had DM; 8 had type I DM and 9 had type II DM. The patients’ average age was 63 (one patient was 33 years old, and the others ranged from 58 to 81 years). There were 10 females and 8 males. The patients were divided into two groups. Five of the 18 patients were extremely difficult to treat and were included in the “severe” group. They were hospitalized for 3 to 5 months (one died after 6 months because of cardiac disease). Each of these patients underwent two to three extensive operations (any one or a combination of radical mastoidectomy, temporomandibular joint (TMJ) excision, parotidectomy, partial removal of the zygomatic arch, and bony/soft tissue debridement of the infratemporal fossa and skull base). Three developed deep fungal infection during the antibiotic treatment and were treated with amphotericin B. Two had transient renal failure due to this treatment. Two developed disturbance of liver functions after treatment with itraconazole. All five had at least one cranial nerve palsy. All these patients had type I DM. The remaining 13 patients were included in the “nonsevere” group. They were treated as inpatients for less than 3 months (2 to 10 weeks) and responded well to antibiotics. None underwent extensive surgery. Some had debridement of external auditory canal granulations. After reviewing the CT scans a severity scale was created based on the different affected areas (Table 1). Some areas were divided into four grades of severity (0-3), others to fewer grades due to a narrower spectrum of findings. For example, at the base of skull two grades were assigned, 0 for no involvement and 1 for bone destruction, whereas the spectrum of pathological find-
ings in the external auditory canal allowed four grades. The CT scans were graded independently by a senior radiologist and a senior otologist and the inter-rater reliability was analyzed using Kappa statistics. Substantial (good) agreement was found for most CT areas graded ( ranging from 0.52 to 0.76). Mean severity scoring was compared between the different patient groups applying the Mann-Whitney rank-sum test. Positive Tc scan rates of the two groups were also compared applying the 2 and t test.
RESULTS In CT scans on average, the “severe” patient group had significantly higher scores in most areas examined (Table 2). Of the 18 patients, 90% had involvement (of any degree) of the external canal, tympanic cavity, mastoid, and nasopharynx, while only 30% had some degree of involvement of the bony areas (TMJ, temporal bone, and skull base) and the parotid gland (P ⬍ 0.005). Most of the patients with bony and parotid disease belonged to the “severe” group. All five “severe” patients had destruction in all three bony areas mentioned above. Four of the “nonsevere” group (31%) had one bony area involvement; the rest had no bone destruction. Tc scan results showed that all five patients in the “severe” group had a positive scan, while in the “nonsevere” group 8 out of 13 (62%) had a positive scan. No statistical tests yielded a significant P value, probably due to the low number of patients, even though a remarkable difference is seen between the rates of positive scans in the two groups. In a slightly larger group a statistical significance would probably have been reached. Another finding, not related to imaging, was that type I DM patients had a higher risk (3.1:1) for a severe disease than those with type II DM (P ⬍ 0.05).
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Stratification for malignant external otitis
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Table 2 Average severity grades and overall number of areas involved (by CT)
Nonsevere (av) ⫾ SD (n⫽13) Severe (av) ⫾ SD (n⫽5) P value
Ext. canal
Middle ear
Mastoid
Parotid gland
Nasopharynx
Temp. bone
TMJ
Skull base
Overall areas
1.8 0.95 2.3 0.67 NS
1.5 1.21 2.9 0.32 ⬍0.05
1.6 1.06 3.0 0.00 ⬍0.05
0.1 0.43 0.5 0.85 NS
0.7 0.87 1.9 1.10 ⬍0.01
0.3 0.88 1.1 0.99 ⬍0.05
0.3 0.60 1.3 0.67 ⬍0.001
0.2 0.37 0.8 0.42 ⬍0.0005
2.9 1.32 5.4 1.07 ⬍0.0005
av, average; SD, standard deviation; NS, nonsignificant; n, number of patients; TMJ, temporomandibular joint.
DISCUSSION We describe 18 MEO (SBO and NEO) patients’ CT findings and Tc scan results. It appears that the initial CT findings of the patients we characterized as “severe” had features that could differentiate them from the “nonsevere” ones. Rubin and Gold, using CT and MRI, demonstrated the involvement rates of the disease in different anatomical areas.11-13 In their studies, most of the pathologic findings were localized to the external auditory canal, tympanic cavity, and the mastoid air cells. Moderate rates of involvement were seen in soft tissue areas of the infratemporal fossa, nasopharynx, and parapharyngeal space. The lowest rates of involvement were in the bony areas such as the petrous bone, TMJ, and base of skull. In addition, Rubin showed that the average number of the above-mentioned areas involved in the disease was three in mild cases and eight in the severe ones.12 Our results were similar. Both groups (“nonsevere” and “severe”) had a similar high degree of disease in the external auditory canal, as expected in MEO. On average, the latter group had a twofold greater severity score in the tympanic cavity and mastoid (P ⬍ 0.05). Some degree of involvement in the nasopharynx was found in most of the 18 patients. The “severe” group had a 2.7-fold higher score than the “nonsevere” (P ⬍ 0.01). This may represent a common and early involvement of the parapharyngeal space. On the other hand, in the parotid gland some degree of involvement was noted in only 30% of the 18 patients, while no significant difference in the severity score was found between the two groups. This may be due to late involvement of the parotid, mainly in severe disease. In the bony areas, we found involvement mainly in the bony external canal, scutum, the TMJ, and base of skull. The average severity score in the “severe” group was up to fourfold greater than the “nonsevere” group; the statistical significance increased as the involved area became deeper (P ⬍ 0.05, 0.001, 0.0005, respectively). The “severe” patients had more involved areas than the “nonsevere” ones (P ⬍ 0.0005) as shown before.12 The severity grades of the CT findings seemed to correlate well with the patients’ grouping. The Tc scan results, on the other hand, did not show significant difference between the two groups.
Levenson et al suggested a classification system for the severity of disease based on Tc scan findings.8 According to their classification system, in patients with “Pre-MEO” the Tc scan was negative, in “Limited MEO” the Tc scan was positive, and in “Central MEO” the Tc scan was positive with disease spreading into the TMJ, skull base, parapharyngeal space, and infratemporal fossa. Patients with cranial nerve palsies were also included in the “central” group. All 10 patients in this study (6 with “central” and 4 with “limited” disease) were free of disease following antibiotic treatment (ciprofloxacin). The authors suggested that 10 to 14 days of ciprofloxacin combined with semi-synthetic penicillin may control the infection, especially in “central” MEO.8 It has been shown that scintigraphy detects inflammatory changes earlier than CT and seems to be more specific for follow-up evaluation.14 On the other hand, initial CT is important since it shows the anatomical extent of the disease15 and small cortical erosions.13 In Levenson’s study the patients were classified according to the Tc scan results and all were cured following ciprofloxacin treatment.8 In our study the “nonsevere” group also responded well to antibiotics. All our “severe” patients did not respond to prolonged antibiotic treatment and needed extensive operations. It appears clinically that Levenson’s patients, classified as “central” MEO (with positive Tc scan in the skull base), would belong to our “nonsevere” patient group. This raises the notion that the appearance of osteomyelitis on CT suggests a much more severe disease than positive scintigraphy does. We found CT to be an important tool for further stratifying MEO patients to “severe” and “nonsevere” at early stages of the disease. In this series MRI was conducted only in five patients. This was done in order to assess soft-tissue spread of the disease and specifically intracranial involvement prior to undertaking extensive surgical procedures. In the last years our threshold for obtaining MRI studies in these patients has become much lower. It has been shown15 that MRI in these patients is important in defining soft-tissue involvement, including meninges and the parotid area, although it is inferior to CT in detecting bony changes. In general, MRI is useful if there are central skull base involvement and cranial nerve palsies. It may be complementary to CT in these cases.
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The course of disease in the “severe” group, although comprising only a small number of patients, led us to reconsider the policy of preliminary antibiotic treatment without early surgical intervention. The questions at hand were whether this policy led these patients to deteriorate in their course, and could a different method of treatment offer a better outcome. Since some patients appear after failure of an ambulatory treatment trial, they may have a profound involvement of the disease on the day of admission, requiring extensive treatment that may include surgery. Another consideration is the rising resistance of pseudomonas to ciprofloxacin.16 In this study, the presence of bony destruction on the initial CT scan and I DM seemed to best define the “severe” group. We propose that after primary classification of patients by Tc scans to SBO and NEO, further stratification using CT should take place in order to identify, at an early stage, patients with potentially severe course of disease.
Stratification Method We suggest stratification of MEO with a score of four points: one for type I DM and one for bone destruction in each of the three following areas: temporal bone, base of skull, and TMJ. When applying this score retrospectively to our study group we found that none of the patients in the “nonsevere” group scored more than two points and all the patients in the “severe” group scored over two points. We suggest that this CT-based severity score should be considered as one of the factors influencing the therapeutic approach to these patients. Patients scoring zero to two points may be considered for antibiotic therapy only (with minimal surgery in the external auditory canal), while those scoring three to four points may be considered for a more aggressive treatment by early surgery and debridement of all affected areas, combined with multiple antipseudomonal therapies. We offer the early surgery approach since in our experience antibiotics alone had a limited effect on the “severe” patients. But it should be stressed that this study cannot provide strong evidence or support for the efficacy of this approach due to its retrospective nature, the relatively small number of patients, and confounding factors such as type I diabetes. The need for surgery in MEO was addressed before by Benecke, who defined it as a “medical, not surgical, disease,”9 and even Levenson’s “central MEO” patients mentioned above responded well to antibiotics only.8 Others, however, stressed the need to combine antibiotic therapy and surgery in face of the rising resistance of pseudomonas to ciprofloxacin,16 and particularly for removal of bone sequestration or bony necrotic areas that may aid the antibiotic activity.17 This methodology proved successful in new cases of MEO at our institution, admitted after we summarized our scoring system. A limitation of this stratification system is that it does not take into consideration the extent of spread. For example, if cranial nerves are involved or CT scan shows extended osteomyelitis of the skull base while other bony areas are intact, then this case should probably belong to the severe group.
Another modality used as an adjunct treatment for MEO, the hyperbaric oxygen, may improve the antibiotic action, especially in refractory cases,17 although recent research revealed no evidence to demonstrate its efficacy and possible complications.18
CONCLUSION MEO patients may appear with a widespread disease, and therefore are prone to a difficult course of disease and complications. We believe that CT can identify these patients in early stages. For the primary identification of bony involvement Tc scan is most appropriate, as prior studies showed. For the secondary stratification to “nonsevere” and “severe” patients, this study suggests a four-point method based on the initial CT, which should be considered as one of the factors determining therapeutic approach in these patients. Further multi-center prospective randomized controlled studies are needed to compare the outcome of early surgical intervention and conservative treatment in order to establish new treatment protocols.
AUTHOR INFORMATION From the Department of Otolaryngology–Head and Neck Surgery (Drs Peleg, Perez, and Cohen), Infectious Diseases Unit (Dr Raveh), and Department of Radiology (Dr Berelowitz), Shaare Zedek Medical Center. Affiliated with the Faculty of Health Sciences, Ben-Gurion University of the Negev. Corresponding author: Ronen Perez, MD, Director, Otology Unit, Department of Otolaryngology-Head and Neck Surgery, Shaare Zedek Medical Center, P. O. Box 3235, Jerusalem, Israel. E-mail address: [email protected].
FINANCIAL DISCLOSURE None.
REFERENCES 1. Chandler JR. Malignant external otitis. Laryngoscope 1968;78:1257– 94. (Grade C). 2. Amorosa L, Mondugo GC, Pirodda A. Malignant external otitis: review and personal experience. Acta Otolaryngol (Stockh) 1996; (Suppl) 521:3–16. (Grade C). 3. Rubin-Grandis J, Branstetter BF 4th, Yu VL. The changing face of malignant (necrotizing) external otitis: clinical, radiological and anatomic correlations. Lancet Infect Dis 2004;4:34 –9. 4. Corey JP, Levandowski RA, Panwalker AP. Prognostic implications of therapy for necrotizing external otitis. Am J Otol 1985;6:353– 8. 5. Cohen D, Friedman P. The diagnostic criteria of malignant external otitis. J Laryngol Otol 1987;101:216 –21. 6. Babiatzki A, Sade J. Malignant external otitis. J Laryngol Otol 1987; 101:205–10. (Grade B). 7. Sade J, Lang R, Goshen S, et al. Ciprofloxacin treatment of malignant external otitis. Am J Med 1987;87(Suppl 5A):138S:141. (Grade B).
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Stratification for malignant external otitis
8. Levenson MJ, Parisier SC, Dolinsky J, et al. Ciprofloxacin: drug of choice in the treatment of malignant external otitis (MEO). Laryngoscope 1991;101:821– 4. (Grade C). 9. Benecke JE. Management of osteomyelitis of the skull base. Laryngoscope 1989;99:1220 –3. (Grade B). 10. Slattery WH 3rd, Brackmann DE. Skull base osteomyelitis (malignant external otitis). Otolaryngol Clin North Am 1996;29:795– 806. 11. Gold S, Som PM, Lucente FE. Radiographic findings in progressive necrotizing “malignant” external otitis. Laryngoscope 1984;96:363– 6. (Grade B). 12. Rubin J, Curtin HD, Yu VL. Malignant external otitis: utility of CT in diagnosis and follow up. Radiology 1990;174:391– 4. (Grade B). 13. Rubin-Grandis J, Curtin HD, Yu VL. Necrotizing (malignant) external otitis: prospective comparison of CT and MR imaging in diagnosis and follow-up. Radiology 1995;196:499 –504. (Grade B).
305 14. Strashum AM, Nejatheim M, Goldsmith SJ. Malignant external otitis: early scintigraphic detection. Radiology 1984;150:541–5. (Grade B). 15. Okapala NCE, Siraj QH, Nilssen E, et al. Radiological and radionuclide investigation of malignant external otitis. J Laryngol Otol 2005; 119:71–5. (Grade C). 16. Berenholz L, Katzenell U, Harell M. Evolving resistant pseudomonas to ciprofloxacin in malignant otitis externa. Laryngoscope 2002;112: 1619 –22. (Grade C). 17. Magliulo G, Varacalli S, Ciofalo A. Osteomyelitis of the skull base with atypical onset and evolution. Ann Otol Rhinol Laryngol 2000; 109:326 –30. (Grade C). 18. Phillips JS, Jones SE. Hyperbaric oxygen as an adjuvant treatment for malignant otitis externa. Cochrane Database Syst Rev 2005(2), CD004617. (Grade A).
ORIGINAL RESEARCH
Stratification for malignant external otitis Uri Peleg, MD, Ronen Perez, MD, David Raveh, MD, Daniel Berelowitz, MD, and David Cohen, MD, Jerusalem, Israel OBJECTIVE: To propose a CT-based method for early identification of severe cases of malignant external otitis (MEO) by correlating between initial CT findings and clinical course. STUDY DESIGN AND SETTING: Eighteen MEO patients who underwent CT on admission were included in this retrospective study conducted at a tertiary center. The number and extent of anatomical areas involved according to CT were compared to clinical course severity. RESULTS: The patients were categorized into two groups according to clinical course. There were 13 patients in the “nonsevere” group and 5 in the “severe.” In six out of eight CT anatomical areas the “severe” group had significantly higher scores (P ⬍ 0.05 to P ⬍ 0.0005). The average number of areas involved in the “nonsevere” group was 2.9 and in the “severe” 5.4 (P ⬍ 0.0005). CONCLUSION: We found a clear correlation between clinical course and initial CT findings in MEO patients. Based on these findings it may be possible to predict clinical course severity according to initial CT. © 2007 American Academy of Otolaryngology–Head and Neck Surgery Foundation. All rights reserved.
T
he term “malignant external otitis” (MEO) was coined by Chandler in 1968 to describe a life-threatening infection of the ear and skull base.1 Since then, the knowledge of the disease on one hand, and the antibiotic treatment on the other, has improved markedly. Therefore, the diagnosis is usually made in the early stages and in many cases the course of disease is less dramatic.2,3 The common diagnostic criteria in most studies include severe otalgia which worsens at night, prolonged external otitis unresponsive to local treatment, external auditory canal granulations, pseudomonas aeruginosa in cultures, diabetes mellitus (DM) or other immune suppression, and a positive bone scan.4-8 MEO was divided by Benecke into necrotizing otitis externa (NOE), in which only soft tissues and cartilage are involved, and skull base osteomyelitis (SBO), in which temporal or skull base bones are involved.9 On the other hand, Slattery and Brackmann used the term SBO as a substitute for MEO.10 This classification is useful for determining the length of treatment.9 Further staging methods were offered using mainly clinical criteria (cranial nerves and intracranial involvement),4
while others used Gallium (Ga) and Technecium (Tc) scans for staging,9 or a combination of bone scan and clinical findings.8 During the nineties we treated five patients who required prolonged hospitalization and numerous extensive operations. It is their course of disease, as well as the CT findings on admission, which led to this study. Our aim was to offer a method by which MEO patients may be stratified to those with potentially severe disease and those with mild disease, by correlating the initial CT results with the clinical course of disease. “Severe disease,” according to our stratification, may be considered as one of the factors influencing the decision for early surgical intervention as an adjunct to antibiotic therapy.
PATIENTS AND METHODS Between the years 1990 and 2000, 18 patients diagnosed with MEO underwent CT and Tc scan on admission. Their medical files and imaging were retrospectively analyzed with the approval of the Institutional Review Board. All our MEO patients fulfilled the common diagnostic criteria mentioned above and were treated as inpatients. We were able to retrieve the CT and Tc scan results of all the patients, but Ga scans of only two patients. Tc and Ga scans were used to distinguish between patients with skull base osteomyelitis and those with soft-tissue inflammation. A high-resolution CT of the temporal bone followed by a CT with contrast media (for soft tissue areas) was obtained. MRI was performed only in five patients, when a more accurate delineation of soft tissue or evaluation of intracranial involvement was needed (usually to aid surgical considerations). We initiated antibiotic treatment immediately after obtaining cultures, with a combination of a fluoroquinolone (usually ciprofloxacin) and an anti-pseudomonal cephalosporin (usually ceftazidime). Local treatment included daily external canal suction and fluoroquinolone drops. Debridement of inflamed tissues was performed when needed. Prior to obtaining the results of the present study, more extensive surgery was reserved only for patients with nonrespon-
Received December 12, 2006; accepted February 20, 2007.
0194-5998/$32.00 © 2007 American Academy of Otolaryngology–Head and Neck Surgery Foundation. All rights reserved. doi:10.1016/j.otohns.2007.02.029
302
Otolaryngology–Head and Neck Surgery, Vol 137, No 2, August 2007
Table 1 Scoring method of the CT findings by their severity at each area Severity score Area
0
1
2
3
External canal Mastoid Middle ear Nasopharynx Parotid Temporal bone* TMJ Skull base
NI NI NI NI NI NI NI NI
Mild thickening Mucosal thickening Mucosal thickening Mild asymmetry, ET open Mild swelling/infiltration Bone destruction Enlarged joint space Bone destruction
Moderate thickening Fluid & air Fluid & air Mild asymmetry, ET thickened/closed Severe swelling/infiltration – Bone destruction –
Passage closed Almost full Almost full Severe asymmetry – – – –
NI, no involvement; ET, Eustachian tube; TMJ, temporomandibular joint. *Temporal bone includes bony external canal and scutum.
sive extensive disease after 4 weeks of the above-mentioned medical treatment, for rapidly expanding disease, or when cranial nerve involvement appeared. Termination of inpatient treatment was determined mainly by clinical improvement and negative cultures, and aided by imaging (CT and bone scans). Seventeen out of the 18 patients had DM; 8 had type I DM and 9 had type II DM. The patients’ average age was 63 (one patient was 33 years old, and the others ranged from 58 to 81 years). There were 10 females and 8 males. The patients were divided into two groups. Five of the 18 patients were extremely difficult to treat and were included in the “severe” group. They were hospitalized for 3 to 5 months (one died after 6 months because of cardiac disease). Each of these patients underwent two to three extensive operations (any one or a combination of radical mastoidectomy, temporomandibular joint (TMJ) excision, parotidectomy, partial removal of the zygomatic arch, and bony/soft tissue debridement of the infratemporal fossa and skull base). Three developed deep fungal infection during the antibiotic treatment and were treated with amphotericin B. Two had transient renal failure due to this treatment. Two developed disturbance of liver functions after treatment with itraconazole. All five had at least one cranial nerve palsy. All these patients had type I DM. The remaining 13 patients were included in the “nonsevere” group. They were treated as inpatients for less than 3 months (2 to 10 weeks) and responded well to antibiotics. None underwent extensive surgery. Some had debridement of external auditory canal granulations. After reviewing the CT scans a severity scale was created based on the different affected areas (Table 1). Some areas were divided into four grades of severity (0-3), others to fewer grades due to a narrower spectrum of findings. For example, at the base of skull two grades were assigned, 0 for no involvement and 1 for bone destruction, whereas the spectrum of pathological find-
ings in the external auditory canal allowed four grades. The CT scans were graded independently by a senior radiologist and a senior otologist and the inter-rater reliability was analyzed using Kappa statistics. Substantial (good) agreement was found for most CT areas graded ( ranging from 0.52 to 0.76). Mean severity scoring was compared between the different patient groups applying the Mann-Whitney rank-sum test. Positive Tc scan rates of the two groups were also compared applying the 2 and t test.
RESULTS In CT scans on average, the “severe” patient group had significantly higher scores in most areas examined (Table 2). Of the 18 patients, 90% had involvement (of any degree) of the external canal, tympanic cavity, mastoid, and nasopharynx, while only 30% had some degree of involvement of the bony areas (TMJ, temporal bone, and skull base) and the parotid gland (P ⬍ 0.005). Most of the patients with bony and parotid disease belonged to the “severe” group. All five “severe” patients had destruction in all three bony areas mentioned above. Four of the “nonsevere” group (31%) had one bony area involvement; the rest had no bone destruction. Tc scan results showed that all five patients in the “severe” group had a positive scan, while in the “nonsevere” group 8 out of 13 (62%) had a positive scan. No statistical tests yielded a significant P value, probably due to the low number of patients, even though a remarkable difference is seen between the rates of positive scans in the two groups. In a slightly larger group a statistical significance would probably have been reached. Another finding, not related to imaging, was that type I DM patients had a higher risk (3.1:1) for a severe disease than those with type II DM (P ⬍ 0.05).
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Stratification for malignant external otitis
303
Table 2 Average severity grades and overall number of areas involved (by CT)
Nonsevere (av) ⫾ SD (n⫽13) Severe (av) ⫾ SD (n⫽5) P value
Ext. canal
Middle ear
Mastoid
Parotid gland
Nasopharynx
Temp. bone
TMJ
Skull base
Overall areas
1.8 0.95 2.3 0.67 NS
1.5 1.21 2.9 0.32 ⬍0.05
1.6 1.06 3.0 0.00 ⬍0.05
0.1 0.43 0.5 0.85 NS
0.7 0.87 1.9 1.10 ⬍0.01
0.3 0.88 1.1 0.99 ⬍0.05
0.3 0.60 1.3 0.67 ⬍0.001
0.2 0.37 0.8 0.42 ⬍0.0005
2.9 1.32 5.4 1.07 ⬍0.0005
av, average; SD, standard deviation; NS, nonsignificant; n, number of patients; TMJ, temporomandibular joint.
DISCUSSION We describe 18 MEO (SBO and NEO) patients’ CT findings and Tc scan results. It appears that the initial CT findings of the patients we characterized as “severe” had features that could differentiate them from the “nonsevere” ones. Rubin and Gold, using CT and MRI, demonstrated the involvement rates of the disease in different anatomical areas.11-13 In their studies, most of the pathologic findings were localized to the external auditory canal, tympanic cavity, and the mastoid air cells. Moderate rates of involvement were seen in soft tissue areas of the infratemporal fossa, nasopharynx, and parapharyngeal space. The lowest rates of involvement were in the bony areas such as the petrous bone, TMJ, and base of skull. In addition, Rubin showed that the average number of the above-mentioned areas involved in the disease was three in mild cases and eight in the severe ones.12 Our results were similar. Both groups (“nonsevere” and “severe”) had a similar high degree of disease in the external auditory canal, as expected in MEO. On average, the latter group had a twofold greater severity score in the tympanic cavity and mastoid (P ⬍ 0.05). Some degree of involvement in the nasopharynx was found in most of the 18 patients. The “severe” group had a 2.7-fold higher score than the “nonsevere” (P ⬍ 0.01). This may represent a common and early involvement of the parapharyngeal space. On the other hand, in the parotid gland some degree of involvement was noted in only 30% of the 18 patients, while no significant difference in the severity score was found between the two groups. This may be due to late involvement of the parotid, mainly in severe disease. In the bony areas, we found involvement mainly in the bony external canal, scutum, the TMJ, and base of skull. The average severity score in the “severe” group was up to fourfold greater than the “nonsevere” group; the statistical significance increased as the involved area became deeper (P ⬍ 0.05, 0.001, 0.0005, respectively). The “severe” patients had more involved areas than the “nonsevere” ones (P ⬍ 0.0005) as shown before.12 The severity grades of the CT findings seemed to correlate well with the patients’ grouping. The Tc scan results, on the other hand, did not show significant difference between the two groups.
Levenson et al suggested a classification system for the severity of disease based on Tc scan findings.8 According to their classification system, in patients with “Pre-MEO” the Tc scan was negative, in “Limited MEO” the Tc scan was positive, and in “Central MEO” the Tc scan was positive with disease spreading into the TMJ, skull base, parapharyngeal space, and infratemporal fossa. Patients with cranial nerve palsies were also included in the “central” group. All 10 patients in this study (6 with “central” and 4 with “limited” disease) were free of disease following antibiotic treatment (ciprofloxacin). The authors suggested that 10 to 14 days of ciprofloxacin combined with semi-synthetic penicillin may control the infection, especially in “central” MEO.8 It has been shown that scintigraphy detects inflammatory changes earlier than CT and seems to be more specific for follow-up evaluation.14 On the other hand, initial CT is important since it shows the anatomical extent of the disease15 and small cortical erosions.13 In Levenson’s study the patients were classified according to the Tc scan results and all were cured following ciprofloxacin treatment.8 In our study the “nonsevere” group also responded well to antibiotics. All our “severe” patients did not respond to prolonged antibiotic treatment and needed extensive operations. It appears clinically that Levenson’s patients, classified as “central” MEO (with positive Tc scan in the skull base), would belong to our “nonsevere” patient group. This raises the notion that the appearance of osteomyelitis on CT suggests a much more severe disease than positive scintigraphy does. We found CT to be an important tool for further stratifying MEO patients to “severe” and “nonsevere” at early stages of the disease. In this series MRI was conducted only in five patients. This was done in order to assess soft-tissue spread of the disease and specifically intracranial involvement prior to undertaking extensive surgical procedures. In the last years our threshold for obtaining MRI studies in these patients has become much lower. It has been shown15 that MRI in these patients is important in defining soft-tissue involvement, including meninges and the parotid area, although it is inferior to CT in detecting bony changes. In general, MRI is useful if there are central skull base involvement and cranial nerve palsies. It may be complementary to CT in these cases.
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The course of disease in the “severe” group, although comprising only a small number of patients, led us to reconsider the policy of preliminary antibiotic treatment without early surgical intervention. The questions at hand were whether this policy led these patients to deteriorate in their course, and could a different method of treatment offer a better outcome. Since some patients appear after failure of an ambulatory treatment trial, they may have a profound involvement of the disease on the day of admission, requiring extensive treatment that may include surgery. Another consideration is the rising resistance of pseudomonas to ciprofloxacin.16 In this study, the presence of bony destruction on the initial CT scan and I DM seemed to best define the “severe” group. We propose that after primary classification of patients by Tc scans to SBO and NEO, further stratification using CT should take place in order to identify, at an early stage, patients with potentially severe course of disease.
Stratification Method We suggest stratification of MEO with a score of four points: one for type I DM and one for bone destruction in each of the three following areas: temporal bone, base of skull, and TMJ. When applying this score retrospectively to our study group we found that none of the patients in the “nonsevere” group scored more than two points and all the patients in the “severe” group scored over two points. We suggest that this CT-based severity score should be considered as one of the factors influencing the therapeutic approach to these patients. Patients scoring zero to two points may be considered for antibiotic therapy only (with minimal surgery in the external auditory canal), while those scoring three to four points may be considered for a more aggressive treatment by early surgery and debridement of all affected areas, combined with multiple antipseudomonal therapies. We offer the early surgery approach since in our experience antibiotics alone had a limited effect on the “severe” patients. But it should be stressed that this study cannot provide strong evidence or support for the efficacy of this approach due to its retrospective nature, the relatively small number of patients, and confounding factors such as type I diabetes. The need for surgery in MEO was addressed before by Benecke, who defined it as a “medical, not surgical, disease,”9 and even Levenson’s “central MEO” patients mentioned above responded well to antibiotics only.8 Others, however, stressed the need to combine antibiotic therapy and surgery in face of the rising resistance of pseudomonas to ciprofloxacin,16 and particularly for removal of bone sequestration or bony necrotic areas that may aid the antibiotic activity.17 This methodology proved successful in new cases of MEO at our institution, admitted after we summarized our scoring system. A limitation of this stratification system is that it does not take into consideration the extent of spread. For example, if cranial nerves are involved or CT scan shows extended osteomyelitis of the skull base while other bony areas are intact, then this case should probably belong to the severe group.
Another modality used as an adjunct treatment for MEO, the hyperbaric oxygen, may improve the antibiotic action, especially in refractory cases,17 although recent research revealed no evidence to demonstrate its efficacy and possible complications.18
CONCLUSION MEO patients may appear with a widespread disease, and therefore are prone to a difficult course of disease and complications. We believe that CT can identify these patients in early stages. For the primary identification of bony involvement Tc scan is most appropriate, as prior studies showed. For the secondary stratification to “nonsevere” and “severe” patients, this study suggests a four-point method based on the initial CT, which should be considered as one of the factors determining therapeutic approach in these patients. Further multi-center prospective randomized controlled studies are needed to compare the outcome of early surgical intervention and conservative treatment in order to establish new treatment protocols.
AUTHOR INFORMATION From the Department of Otolaryngology–Head and Neck Surgery (Drs Peleg, Perez, and Cohen), Infectious Diseases Unit (Dr Raveh), and Department of Radiology (Dr Berelowitz), Shaare Zedek Medical Center. Affiliated with the Faculty of Health Sciences, Ben-Gurion University of the Negev. Corresponding author: Ronen Perez, MD, Director, Otology Unit, Department of Otolaryngology-Head and Neck Surgery, Shaare Zedek Medical Center, P. O. Box 3235, Jerusalem, Israel. E-mail address: [email protected].
FINANCIAL DISCLOSURE None.
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