EXPERIENCE AND REASON |
Bullous Myringitis: A Case-Control Study
Division of General Academic Pediatrics, University of Texas Medical Branch at Galveston, Galveston, TX 77555-1119
Division of Education/Research, University of Texas Medical Branch at Galveston, Galveston, TX 77555-0344
Department of Otolaryngology, Children’s Hospital, Denver, CO 80218
University of Texas Medical Branch at Galveston, Galveston, TX 77555-1119
Division of Infectious Diseases, University of Texas Medical Branch at Galveston, Galveston, TX 77555-0371
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ABSTRACT |
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Prior studies have shown that bullous myringitis (BM) accounts for <10% of acute otitis media (AOM) cases, and that the distribution of viral and bacterial pathogens in BM is similar to that in AOM without BM, except for a relative increase in the proportion of Streptococcus pneumoniae in BM. We studied 518 cases of AOM in children aged 6 months to 12 years. Using tele-otoscopy to assist the diagnosis, we identified 41 cases (7.9%) with BM. Children who had AOM with BM were older than AOM patients without BM (median age: 4.3 years vs 18 months). We compared 41 cases of AOM with BM to 41 control cases of age-, race-, and gender-matched AOM patients without BM. When compared with this matched control group, children with BM had more severe symptoms at the time of diagnosis and were more likely to have bulging of the tympanic membrane in the quadrants that were not obscured by the bulla. Children with AOM and BM may require aggressive pain management. Although parents and clinicians may agree that a watchful waiting approach is appropriate for older children with mild AOM, children experiencing painful AOM with BM may not be successful candidates for a watchful-waiting approach, because parents may resist postponement of antibiotic therapy in children who are more symptomatic.
Key Words: acute otitis media • diagnosis • bullous myringitis • case-control • child
Abbreviations: BM, bullous myringitis • TM, tympanic membrane • AOM, acute otitis media • OM, otitis media • OM-3, otitis media 3-item questionnaire • UTMB, University of Texas Medical Branch at Galveston • OS-8, otoscopy score, 8 grades
Bullous myringitis (BM) is an acutely painful condition of the ear characterized by bulla formation on the tympanic membrane (TM). BM was described in early articles as occurring in association with acute otitis media (AOM).1,2 Previous studies indicated that BM is often associated with fever3 and considerable pain,3,4 possibly because the blisters of BM may occur between the richly innervated outer epithelium and middle fibrous layers of the TM.5,6 Bullae involving the TM may also extend onto portions of the external auditory canal immediately adjacent to the TM.3 Bullae involving the TM should be distinguished from bullae involving only the ear canal; the latter are a form of external otitis media (OM). It was once thought that Mycoplasma pneumoniae infection was an important cause of BM,7–10 but this idea was later invalidated.11–13 In an extensive review of the literature, Merrifield11 identified reports of 612 patients with documented M pneumoniae infection, and among these 37 patients had ear involvement (6 with BM). In reported cases of BM, 1 of 16 grew M pneumoniae. Of 858 attempts to isolate M pneumoniae from non-BM cases of AOM, none grew M pneumoniae from the middle ear fluid. Merrifield concluded that: "The tympanic membrane’s ability to form blisters appears to be a nonspecific reaction. Bullous myringitis is merely acute otitis media with blisters within the layers of the eardrum. There is little evidence that otitis media, with or without bullous myringitis, is caused by Mycoplasma pneumoniae."
Studies have shown that BM accounts for <10% of AOM cases, and that viral and bacterial pathogen distribution in BM is similar to that in AOM without BM, except for a relative increase in the proportion of Streptococcus pneumoniae in ears with bullae.14,15 Although descriptive studies indicate that BM is a severe form of AOM, no quantitative information on the clinical severity of illness has been reported in AOM patients with and without BM. In this case-control study, we compared the clinical severity of AOM with or without BM, based on parent’s perception of illness, body temperature, tympanogram, and otoscopic findings.
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METHODS |
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Subjects
We prospectively recruited a convenience sample of children with symptomatic AOM (aged 6 months to 12 years) from our pediatric clinic. Patients were initially identified if they had signs and symptoms of AOM as described below. Patient enrollment occurred between May 2000 and August 2002. Verbal assent was obtained from parents as approved by our institutional review board. Oral, rectal, or axillary body temperatures were measured by electronic thermometer. All oral and rectal temperatures were corrected to axillary (skin) temperature for the purpose of comparability. Parents completed a demographic questionnaire on risk factors such as duration of breastfeeding (months), day care attendance (not attending, 1–20 hours/week, 21–40 hours/week, >40 hours/week), passive tobacco smoke exposure at home (not exposed or exposed), and prior history of ear infections (number of infections). To be included in the study, children were required to have 1) symptoms, 2) evidence of acute inflammation of the TM, and 3) middle-ear effusion.
Symptoms
All subjects had acute onset of symptoms, signs of TM inflammation, and presence of middle-ear fluid.16 Because a valid and standardized severity scoring method was not available for AOM, we asked parents to report the severity of their child’s ear infection symptoms on a questionnaire (OM-3) that listed the 3 acute illness items from Rosenfeld’s OM health status questionnaire,17 originally designed for children with chronic middle-ear effusion. The OM-3 questionnaire consisted of the following 3 items: "During the past 24 hours, has your child experienced any of the following attributable to ear infection a) physical suffering such as ear pain, ear discomfort, high fever, or poor balance, b) emotional distress such as irritability, frustration, sadness, restlessness, or poor appetite, and c) limitation in activity such as playing, sleeping, doing things with friends/family, attending school or day care." Parents indicated the severity of each of the 3 OM-3 items by marking a 7-point Likert scale from 1 ("not present, not a problem") to 7 ("extreme problem"). The duration of time between the onset of AOM symptoms and the diagnosis was not recorded in this study. OM-3 total scores were calculated as the sum of the 3 items.
We validated OM-3 for use in children with AOM as follows: a) 6 UTMB (University of Texas Medical Branch at Galveston) expert investigators agreed on its face validity, b) OM-3 demonstrated inter-item reliability (
= 0.80; n = 518 children with AOM, where reliability <0.4 = poor, 0.4–0.75 = good, >0.75 excellent), c) higher OM-3 total scores and physical suffering subscores were associated with greater degrees of inflammation of the TM (OM-3 total vs otoscopy score, 8 grades [OS-8], 
5 or 
6, P < .06; physical suffering subscore vs OS-8 5 or 6; P < .001; 
2 test; n = 518), d) higher OM-3 total scores and physical suffering subscores were associated with higher body temperatures, (OM-3 total score vs body temperature, Spearman correlation, R = 0.21; P < .0001; n = 518; physical suffering subscore vs body temperature, R = 0.24; P < .0001; Spearman), and e) correlation between OM-3 total score and 2 previously published symptom-severity scales: a 5-item ear treatment group scale described previously18 (R = 0.66; P < .0001; n = 518; Spearman) and a previously published visual analog scale19,20 (R = 0.73; P < .0001; n = 518, Spearman).
TM
Because none existed previously, we developed, as follows, a categorization system (OS-8) to describe the appearance of the TM in children with AOM.21,22 First, numerous photographs of the TMs of children with and without AOM were obtained by our investigators using a Storz tele-otoscope (Karl Storz Imaging, Goleta, CA) through a 3.0-mm reusable speculum held in place by a Welch Allyn otoscope head (Welch Allyn, Inc, Skaneateles Falls, NY). Photographs were printed in glossy format using a Sony printer (Sony Electronics, Woodcliff Lake, NJ), and saved on a server for future study.
The investigators studied the photographs and sorted them initially into categories from normal (no erythema, no effusion, normal structures) to severe (erythema, effusion, opacification, bulla formation). The investigators then used the grading scale to independently evaluate sets of photographs. At each iteration, the investigators discussed their differences and improved on the definitions. The scale was modified repeatedly until 6 investigators reached verbal agreement on the following 8 levels of severity: 0 = normal, or effusion without hyperemia; 1 = hyperemia only, no effusion; 2 = hyperemia, air-fluid level, no opacification, meniscus noted; 3 = hyperemia, complete effusion, no opacification; 4 = hyperemia, opacification, air-fluid level observed, no bulging; 5 = hyperemia, complete effusion, opacification, and no bulging; 6 = hyperemia, bulging rounded doughnut appearance of TM; and 7 = hyperemia with bulla formation. TMs rated between 2 categories were given the higher score. Because we were using very high-quality examination equipment, we were often able to directly visualize bubbles or a fluid level within the middle-ear space in ears categorized as grade 2 and 4, even when the TM was erythematous and partially opacified. Intense illumination was provided by a hand-held otoscope supplied with a fresh halogen lamp and fully-charged nickel cadmium batteries. We also used the original Welch-Allyn reusable speculum, which we consider superior to the Welch-Allyn disposable speculum, which has numerous design flaws.23
OS-8 was further validated as follows. At pediatric meetings we approached North American pediatricians (27% academic, 60% private, 13% other) who agreed to grade, by order of severity, a set of high-quality prints of the OS-8 photoset displayed in random order. Ninety-five of 122 pediatricians responded to the survey. Statistical analysis of the results confirmed good agreement with our predetermined levels of severity (R = 0.841; P < .001; N = 759 comparisons; Spearman).
Once OS-8 had been developed, investigators were trained to grade the TMs using photosets and live ears of children with AOM until their independent inter-observer agreements reached an acceptable level (Kappa >0.6). The trained investigators then performed otoscopic examinations on the subjects in this study, and graded the TMs using OS-8. Whenever possible, diagnosis was aided by photographs of subjects’ TMs taken with the tele-otoscope. In accordance with expert panel criteria,24 TM opacification was required for inclusion in the study (OS-8 score 4 in at least 1 TM). Because blood vessel dilatation is a manifestation of inflammation, we excluded children from the study if they had no evidence of TM hyperemia. When photographs were available, the bullae were later inspected to verify their color, degree of opacification, location, size, and shape. In addition, any quadrants not occupied by a bulla were observed for the presence of bulging.
Middle-Ear Effusion
Tympanograms were obtained on all subjects using a Welch-Allyn TM262 Auto Tymp tympanometer and were categorized using standard criteria25 except we used a more stringent definition of abnormal compliance (<0.2 mL.) based on results reported by Le et al.26 Tympanograms were classified as: normal, type A (compliance 0.2 mL, –100 < middle-ear pressure +50 daPa); bulging, type A+ (compliance 0.2 mL, middle-ear pressure > +50 daPa); middle-ear effusion, type B (compliance <0.2 mL); and retracted, type C (compliance 0.2 mL, middle ear pressure < –99 daPa). For a diagnosis of AOM, children were required to have evidence of middle-ear effusion by pneumatic otoscopy and/or tympanometry and/or direct visualization of a fluid level. Effusions observed in ears with a normal tympanogram were typically characterized by the presence of either: a) a fluid-filled bulla or bullae on a hyperemic opacified TM, or b) a nonbulging hyperemic TM that under high illumination showed a partial effusion, ie, an air-fluid level (opaque fluid) or air bubble(s).
Chart Review
Charts of the cases and controls were reviewed for follow-up course of the illness and evidence of prior S pneumoniae heptavalent vaccine administration (Prevnar, Wyeth Laboratories, Madison, NJ). Subjects were categorized as immunized if at least 1 month had elapsed between their last immunization and enrollment in the study. S pneumoniae type-specific antibody titers were considered high enough to provide partial or complete protection if a) the first dose of vaccine was given between the ages of 2 and 12 months, and the child had received at least 3 doses, or b) if the first dose of vaccine was given between the ages of 1 and 2 years, and the child had received 2 doses, or c) if a single dose of vaccine was given 2 years of age. Subjects were categorized as not immunized if they had not received vaccine or had received any number of doses less than the regimen described above. Children began receiving heptavalent pneumococcal vaccine in our clinic in October 2000.
Statistics
Forty-one of 518 cases of AOM were diagnosed with BM (7.9%). Because the subjects with BM (median age: 4.3 years) were older than the subjects without BM (median age: 18 months), each subject with BM was paired with his/her closest AOM case without BM, matched by age, race, and gender. The median difference in ages between the subjects with BM and their matches was 7 weeks. We used the t test to compare total OM-3 scores of the subjects with and without BM and the paired t test to compare physical suffering scores for subjects with BM and their matches (SAS statistical software). We used the 2 test to evaluate the relation of bulla formation to categorical variables such as exposure to tobacco smoke (none vs any smokers at home), season of diagnosis (November–February vs March–October), and type of tympanogram. We used the sign test27 to compare the groups on all other variables. A P value < .05 was considered to be statistically significant. If bilateral AOM were present, only data from the worst ear (considering the OS-8 score and tympanogram) were analyzed.
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RESULTS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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Of 41 matched pairs, 51% were male; 39% were white, 27% Hispanic, 24% black, and 10% other. Bilateral AOM was present in 29% of the BM subjects and 32% of the non-BM subjects. Two of the 41 BM cases had bilateral BM. Two of the 41 BM cases (5%) and 5 of the 41 non-BM controls (12%) displayed a normal (type A) tympanogram. Five of the BM cases and 1 of the non-BM cases displayed an A+ or positive pressure tympanogram. These comparisons were not statistically significant by
2 analysis (see Table 1). Total mean OM-3 scores were 13.5 ± 4.7 for the BM cases and 12.1 ± 4.1 for the non-BM controls (P = .05). The difference in OM-3 total scores between the groups was attributable mainly to the physical suffering subscore. The mean physical suffering subscore was 4.76 in subjects with AOM and BM, versus 4.27 in subjects with AOM and non-BM, a difference of 0.49 units or 0.29 standard deviation (P < .02; Table 2). BM was not associated with duration of breastfeeding, day care attendance, passive tobacco smoke exposure, or prior history of ear infections. Mean skin surface body temperatures were marginally higher in the BM group (BM subjects mean: 36.7 ± 0.83°C; non-BM subjects mean: 36.4 ± 0.73°C; P = .06; see Table 2). Nine subjects with BM had 37.3°C (equivalent to 38.3 rectal temperature) at the time of initial evaluation; 4 subjects in the non-BM group had initial temperatures this high.
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Distribution of OS-8 scores for the non-BM matched controls was as follows: 13 with a score of 4 (32%), 11 with a score of 5 (26%), and 17 with a score of 6 (42%). Bulging of the portions of the TM not occupied by the bulla was not initially recorded for any subject receiving an OS-8 score of 7. However, photographs were available for review in 33 subjects with AOM and BM (see Fig 1, Fig 2, and Fig 3); of these 32 (97%) had a bulging TM. Only 17 of 41 (42%) of the non-BM pairs had a bulging TM.
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Three of the 41 cases of AOM with BM were diagnosed with draining OM 22 to 60 days after initial evaluation. This compares with one case of draining OM on the 51st day after evaluation among the non-BM controls. There were no differences in history of tympanostomy tube placement, failure of treatment, or relapse between the BM cases and non-BM controls. Only 7% percent of the BM cases and 10% of the non-BM matched controls had received sufficient numbers of doses of heptavalent pneumococcal vaccine to meet criteria for partial or complete protection against the strains of S pneumoniae common to children. Neither breastfeeding, tobacco smoke exposure, attendance at child care, history of prior AOM, nor season of diagnosis was related to BM.
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DISCUSSION |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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This study presents quantitative evidence that BM cases may have more severe symptoms than non-BM cases when compared against the broad spectrum of AOM observed in clinical practice. Our data agree with prior studies showing that BM occurs more commonly in older children.13 A strength of this study is the case-control design and the large number of nonbullous AOM subjects available for matching and statistical comparison with the BM subjects. Another strength is the quality of otoscopic examinations performed by trained investigators with assistance of the OS-8 scoring system and high-resolution photographs taken with the tele-otoscope (Figs 1–3).
Because the between-group differences were small for OM-3 and physical suffering (<0.5 standard deviation), additional work will be needed to verify the clinical significance of our findings. However, our findings do support published clinical observations in which authors have described BM as having more severe symptoms than AOM without bulla formation. These results are also supported by the finding that 97% of the TM photographs from the subjects with BM showed bulging of the portions of the TM that were not obscured by the bulla, whereas only 42% in the control group showed bulging of the TM. Bulging is generally considered to be a more severe presentation of AOM.
A possible weakness of the study is the lack of data on the validity of tympanometry for the assessment of middle-ear effusion in AOM. We categorized tympanograms using methods based on articles by Finitzo25 and Le.26 However, these authors did not specifically study subjects with AOM, but assessed children immediately before the insertion of pressure equalizing tympanostomy tubes. Our study emphasizes the need for additional work on the reliability of tympanometry as a specific predictor of middle-ear effusion in AOM.
We and others have previously shown that a middle-ear culture positive for S pneumoniae is often associated with more severe clinical symptoms of AOM, higher levels of inflammatory mediators, and/or otoscopic evidence of a more inflamed TM.28–30 The present study provides no bacteriologic data; however, others have shown that S pneumoniae is more often the etiologic agent in BM than in AOM without BM.14,15 Palmu14 detected S pneumoniae in 32.4% of ears with BM versus 14.5% of ears with no BM. Coffey1 cultured S pneumoniae in 7 of 10 ears with BM. Rosenblut15 detected S pneumoniae in 20 of 27 (74%) cases with BM compared with 43 of 143 (30%) cases of AOM without BM (P < .001). It should be noted that the children with BM in our study were older than the others, and many had not had an opportunity to receive the heptavalent pneumococcal vaccine. We speculate that S pneumoniae might be responsible for the greater degree of inflammation and more severe symptoms in some of our cases as well.
Clinicians have been encouraged to consider an option of watchful waiting using symptom management without prescribing immediate antibiotics for children with mild AOM, because the literature indicates that most such children will recover without antimicrobial treatment.31–32 This approach would facilitate the judicious use of antimicrobial agents currently recommended by the Centers for Disease Control and Prevention.33 Some children experiencing painful AOM with BM may not be successful candidates for a watchful-waiting approach to treatment, because parents may resist postponement of antibiotic therapy in children who are more symptomatic. If antibiotic treatment is initiated for such children, caution should be used in selecting the appropriate agent. The literature indicates that S pneumoniae is more often the pathogen responsible for AOM with BM, and this organism may be resistant to penicillin and other antibiotics in communities where antibiotics have been used extensively.
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CONCLUSIONS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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When compared with children with AOM without BM, children with AOM and BM were older, had higher symptom scores, and had more severe otoscopic findings in the portions of the TM not occupied by the bulla. Because some children with BM may have significant pain at the time of initial evaluation, the clinician should pay special attention to pain management in such cases. Children with painful BM may not be successful candidates for a watchful-waiting approach, because parents may resist postponement of antibiotic therapy in children who are more symptomatic.
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ACKNOWLEDGMENTS |
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This work was supported by grant M01 RR 00073 from the National Center for Research Resources and grant R01 HS10613-02 from the Agency for Healthcare Research and Quality. Eiizabeth Diaz, PA, assisted with data collection, and Mary H. Whitby assisted in preparation of the manuscript.
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FOOTNOTES |
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Received for publication Dec 13, 2003; Accepted Jun 3, 2003.
Reprint requests to (D.P.M.) Department of Pediatrics, Primary Care Pavilion, 400 Harborside Dr, Rm 2.701, Galveston, TX 77555-1119. E-mail: david.mccormick{at}utmb.edu
Davis C. Teichgraeber, BA, is a third-year medical student at the University of Texas Medical Branch at Galveston, Galveston, Texas.
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