The Etiology of Bullous Myringitis and the Role

of Mycoplasmas in Ear Disease: A Review

Donald B. Roberts, MD

From the Department of Pediatrics, Trip/er Army Medical Center, Hawaii 96859

ABSTRACT. A critical review of the literature concerning rial pathogens.

bullous myringitis has found one case of possible myco- This review is an attempt to summarize all the
plasmal, one of possible viral, and 43 ofbactenal, etiology.
English language studies of mycoplasmal, viral, and
The bacteria were Streptococcus pneumoniae, Haemo-
philus influenzae, and $-hemolytic Streptococcus, in the bacterial cultures from patients with MB, and to
same percentages as found in (nonbullous) otitis media. evaluate the importance of Mycoplasma in otitis
One of 858 attempts to isolate Mycoplasma from cases of media in general. Cases in which the specimens for
(nonbullous) otitis media was successful. The evidence culture were obtained by needle aspiration from the
that Mycoplasma are a cause of otitis media with or
ear itself, either blister fluid or fluid from the middle
without bullae is weak. Bullous myringitis probably is not
a separate clinical entity, but merely acute otitis media ear, will be emphasized since cultures from other
with blisters on the eardrum. Pediatrics 65:761-766, 1980; sources, eg, throat, nasopharynx, or drainage from
bullous myringitis, myringitis bullosae, otitis media, my- the ear canal, have been shown to be unreliable in
coplasma pneumoniae. cases of AOM.’23

DEFINITION

Bullous myringitis, as the term is used here, is a

Many reference works describe bullous myringi-
state of the tympanic membrane having vesicles
tis, or “myringitis bullosa,” (MB), as a disease entity
within the substance of the membrane itself. These
seperate from acute otitis media.’’#{176} The etiologic
vesicles, “blebs” or “blisters,” may be single or
agent is generally stated to be Mycoplasma pneu-
multiple, large or small, clear, yellow, or red. For
moniae, the clinical course self-limited, and the
the purposes of this report, the presence of such
preferred treatment symptomatic.
vesicles establishes the diagnosis regardless of the
Other authors have reported cases of acute otitis
appearance of the remainder of the eardrum.
media with blisters on the eardrum.’ ‘‘ This latter
situation is far more common in my experience. In
RESULTS OF CULTURES
eight years of pediatric practice I cannot recall ever
having seen a case of “pure bullous myringitis,” in Attempts to isolate Mycoplasma from ears with
which the nonblistered portion of the eardrum was MB are summarized in Table 1. There are only 16
normal. The nonblistered portion varies in appear- attempts reported, and 15 of these were negative.
ance, as it does in cases ofacute otitis media (AOM), In the single positive case, M pneumoniae was
but usually has clearly visible fluid, often appearing isolated from the fluid aspirated from the bleb.
purulent, behind the drum. Standard bacterial cultures were not reported in
Rowe,’5 in a comprehensive review of acute sup- this case, so it is not known whether this ear was
purative otitis media, concluded that MB should be bacteriologically sterile.
treated the same as AOM without bullae; he cited Table 2 summarizes the 13 reported attempts to
references showing that cultures from middle ear isolate viruses from ears with MB. Twelve of them
aspirates of children with MB usually yield bacte- failed to grow viruses; one grew an adenovirus 3 and
was negative for bacterial growth.
Table 3 summarizes the available information
Received for publication Sept 11, 1978; accepted Aug 10, 1979.
concerning standard bacterial cultures from ears
Reprint requests to (D.B.R.) Department of Pediatrics, Letter-
man Army Medical Center, PSFCA 94129.
with MB. Of the 66 reported aspirations, 43 grew
PEDIATRICS (ISSN 0031 4005). Copyright © 1980 by the bacteria and 40 of these were S pneumoniae, H
American Academy of Pediatrics. influenzae or $-hemolytic Streptococcus, and they

PEDIATRICS Vol. 65 No. 4 April 1 980 761

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TABLE I . Bullous Myringitis: Results of Mpneumoniae Cultures
Method of Sampling Method of Culture No. of No. Source
Cases Positive
Needle aspiration of middle ear PPLO* broth and agar 9 0 Feingold et al”
TiMes et al24
Needle aspiration of middle ear PPLO agar 4 0 Halsted et al’2
Needle aspiration of bleb only Monkey and human kidney 1 0 Rificind et al25
tissue culture, then into
chick embryos and PA
tested
Paracentesis of ear, swab from canal PPLO broth and agar 1 0 Sob#{233}slavsky et al26
Unspecified PPLO broth and agar 1 1 Clyde and Denny2’

Total 16 1
* Abbreviations used are: PPLO, pleuropneumonia-like organisms; FA, fluorescent antibody.

TABLE 2. Bullous Myringitis: Results of Viral Cultures

Method of Sampling Method of Culture No. of Pa- No. Positive Source
tients

Needle aspiration of middle ear MK,* DF, HeLa 9 1 Tifies et al24

(adenovirus 3)
(bacteriologi-
cally sterile)
Needle aspiration of middle ear MK, Hep 2 4 0 Halsted et al’2

Total 13 1
Abbreviations used are: MK, rhesus monkey kidney; Hep-2, human epidermoid carcinoma oflarynx; DF, WI-26 strain
of human diploid fibroblasts.

TABLE 3. Bullou 5 Myringitis: Results of Standard Bacterial Cultures

Method of Sampling S pneumoniae H influ- /3-Hemolytic Other Bacteria Total No Growth No. of Source
enzae Streptococ- Bacteria Cases
cus

Needle aspiration of 0 0 1 0 1 8 9 Lahikainen#{176}

bleb
Needle aspiration of 0 0 1 0 1 8 9

middle ear (same (same (same

case) case) case)
Needle aspiration of 13 5 7 1 26 11 37
middle ear (Streptococcus
viridans)
Needle aspiration of 0 0 0 1 1 0 i Rifldnd et al
bleb (S albus and
diphtheroids)
Needle aspiration of 2 1 2 5 4 9 Feingold et al”
middle ear .

Needle aspiration of 6 3 0 1 10 0 10 Coffey’3

middle ear (usually (Spneumoniae and
through portion un- H influenzae)
involved with bulla
formation)

Totals 21 9 10 3 43 23 66
Percentages 32 14 15 5 65 35 100

were grown in percentages similar to the percent- Table 4 summarizes the cultures for Mycoplasma
ages obtained from a voluminous literature on cul- from ears with abnormalities of a nonbullous na-
tures from AOM. A search of the English language ture. These were considered by the various authors
literature failed to find any other reports of cultures to be either acute otitis media or serous otitis media.
of any kind from ears with MB. Out of a total of 858 such cultures there was one

762 BULLOUS MYRINGITIS

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TABLE 4. Mycoplasma Cultures in Nonbullous Ear Disease
Type of Ear Method of Obtaining Method of Culture No. of No. Source
Cases Positive

“Serous OM” - Not stated PPLO broth and agar 35 0 Sprinkle25

“Acute OM with bulging TMs” Needle aspirate PPLO broth and agar 81 0 Tiles et al24
“Acute middle ear infection” Needle aspiration PPLO broth and agar 563 0 Gr#{246}nroos et al
“Serous OM” Myringotomy and swab PPLO broth and agar 2 1 Sob#{233}slavsky et al26
(also grew Micrococ-
cus albus)
Red, yellow, bulging, 63 Needle aspirate PPLO agar 102 0 Halsted et al’2
Red or gray, minimal bulge,
14
Red, no distortions, 15
Not described, 10
“Bulging TMs” Needle aspirate Mardh and Westrom3#{176} 75 0 Kamme et al3’

Totals 858 1 (swab from external canal)

* Abbreviation used is: OM, otitis media; TMs, tympanic membranes.

positive for M pneumoniae. That was a culture of with meningitis after his fourth attack. Karelitz did
an external canal swab following a myringotomy not do cultures of the ears.
and was not bacteriologically sterile.26 A study by Yoshie is frequently cited as evi-
There is, then, only one published case of the dence that MB can be caused by influenza virus.
aspirate of an ear with MB growing Mpneumoniae Since the study has been quoted so often, it will be
and one growing a virus, in contrast to the 40 of 66 examined in some detail here. Yoshie’s report con-
which grew one or more of the three most common cerned “influenzal otitis media,” which he defined
pathogens in acute purulent otitis media. It is not as .an acute
“. . hemorrhagic otitis media accompa-
known whether the one case positive for M pneu- nied by severe otodynia.” During “a small epidemic
moniae was sterile for the usual bacterial patho- of influenza-like febrile infection. . . .“ there were
gens. 876 outpatients seen in a clinic, 97 of whom had
In spite of the available evidence summarized “otitis media,” and 27 of these had what was
above, many authors continue to state that MB is thought to be “influenzal” otitis media. Yoshie
caused by Mpneumoniae, and that Mpneumoniae chose ten cases to culture out these 27 and isolated
is one of the agents causing AOM. The reasons for viruses in four; he does not state the collection
these statements will be the subject of the following method. Although he states that bacteriologic ex-
discussion. aminations were done, there is no mention of the
results in any of the ear discharges examined; thus
it is impossible to determine whether these were
DISCUSSION OF THE LITERATURE also positive for pathogenic bacteria.
Because of the unspecified appearance of the ears
Role of Viruses
studied, the criteria for selecting the cases for study,
Long before the first description of the Eaton the uncertainty of method of sample collection
agent (pleuropneumonia-like organisms (PPLO), used, and the lack of standard bacteriology reports,
Mycoplasma pneumoniae), MB was thought to be the case for a viral etiology for the otitis itself,
caused by “influenza.”32 There were a number of separate from the accompanying respiratory infec-
published observations that MB accompanied cases tion, is a weak one. The study says nothing about
of clinical influenza. Indeed, MB was sometimes the viral etiology of bullous myringitis.
called “influenzal otitis.” That MB was not neces- Tilles et al24 cultured needle aspirates from nine
sarily specific for influenzal disease was noted over patients with MB and grew an adenovirus 3 from
40 years ago by Karelitz.’ He described the clinical the bacteriologically sterile otitic fluid of one of
appearance, symptoms, and course of 147 cases of them from an 8-year-old child. (In the same study
“myringitis bullosa hemorrhagica” in 87 patients. they grew known bacterial pathogens in five of the
He found that “myringitis bullosa hemorrhagica” nine.)
occurred with a variety of upper respiratory tract
infections including measles. In addition, 17 of Ka-
Role of M pneumoniae
relitz’s patients had purulent drainage, either spon-
taneously or after myringotomy. There were three A study reported by Rifkind et al25 first raised
cases of mastoiditis in children, and one child died the possibility of Mpneumoniae as a cause of MB.

PEDIATRICS
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19, 2019 CLINICIAN 763
This study is widely reported as demonstrating the Couch et al found two cases of MB among 27
Mycoplasma etiology of MB, and has been the volunteers inoculated with tissue culture-propa-
impetus for many subsequent studies. As is often gated M pneumoniae and none in 42 cases inocu-
the case in medical literature, the original study lated with agar-grown M pneumoniae. The ears
was done well, carefully controlled, adequately re- were not cultured. Numerous other cases of natu-
ported, and rationally discussed. The conclusions rally occurring and experimentally-induced Eaton
reached are somewhat tentative, and are so stated. agent ifinesses have had a lower reported incidence
It is the interpretation of this study by subsequent of MB.34#{176}
authors that has been largely responsible for the Table 5 lists six studies of the epidemiology and
belief that a mycoplasmal etiology for MB has been clinical course of Mycoplasma infections. Thirty-
proven. seven of 612 cases were reported to have ear in-
Riflund et al inoculated 52 men, 21 to 36 years of volvement (6%) and at least six of these had MB
age, with an Eaton agent inoculum. Twenty-seven (at least 1%). These figures are certainly lower than
of these men had no prior demonstrable Eaton 13 of 52 in Rifkind’s study alone who developed
agent antibody (titer < 1:10) and 25 had titers of 1: myringitis (25%), and the two of 52 with MB (3.8%).
10 to 1:80. In the group without antibody, 12 devel- There is no obvious explanation for the difference
oped “myringitis” and in the group with antibodies, in the incidence of eardrum involvement among
one developed “myringitis.” The authors state: these studies. Perhaps it was overlooked in some
(yet pharyngitis, posterior cervical adenopathy, ex-
The myringitis was usually bilateral and was accompa-
nied by throbbing pain. Posterior cervical lymphadenop- udate, and mucoid rhinorrhea were duly noted), or
athy was present in four subjects. Ear involvement varied the conditions of or around the experimental sub-
from a mild injection of the tympanic membranes to a jects differed in some unspecified way.
severe inflammatory reaction with edema. In five patients Whatever the reasons for the differences noted,
hemorrhagic areas appeared over the drums and adjacent two of Rifkind’s and two of Couch’s subjects did
membranes. In two of these,
preceded hemorrhage
the develop MB after upper airway inoculation of M
appearance of serous-filled blebs which also later filled pneumoniae. The only sample taken from one of
with blood. There was neither bulging of the membrane the involved ears itself, however, was negative for
nor fluid behind the drum, and spontaneous perforation
M pneumoniae, suggesting, but not proving, that
did not occur.
the M pneumoniae upper airway involvement es-
A bleb in one case was ruptured and cultured- tablished an inflammatory reaction that involved
without success-for Eaton agent. Bacterial cul- the ears, but that Mpneumoniae was not in the ear
tures of the same fluid grew Staphyloccoccus albus itself.
and diphtheroids. The remainder of the ears with Sob#{232}slavsk et al26 are also widely quoted in the
myringitis were not punctured for culture because literature as having demonstrated that M pneumo-
no fluid was seen behind the membrane. The au- niae can cause MB. They reported the Rificind
thors stated that the absence of suppurative disease study as demonstrating that the myringitis ob-
and “the aggregation of these illnesses in the anti- served was “due to” Mpneumoniae. They did state
body-free group support the contention that Eaton that Mycoplasma was not recovered from the ears
agent was responsible for this complication.” of any of Ritkind’s cases, but only from other por-
Thus, Rificind et al found two cases of MB in 27 tions of the respiratory tract. Sob#{233}slavsk then
antibody-negative men inoculated with Eaton reported three cases observed while examining 20
agent. A bleb on one of these ears was cultured for children with the diagnosis of “acute otitis media.”
Eaton agent. It was not grown. One of these three patients had blebs on his ear-
In experimentally-induced respiratory infections, drum, and the other two had eardrums that were

TABLE 5. Ear Involvement in Mycoplasma Infectious

Type of Infection No. of No. Reported with Ear Involvement Source

Patients

Naturally occurring 209 0 Kingston et al’

Experimentally produced 106 2 (“nonsuppurative otitis media”) Curnen et al
Experimentally produced 78 0 Commission on ARD
Naturally occurring 98 20 (“otitis.” At least two cases ofbul- Foy et al37
bus myringitis)
Experimentally produced 52 13 (“myringitis,” two bullous) Rificind et al25
Experimentally produced 69 2 (bullous myringitis) Couch et al

Totals 612 37 (6%)

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“heaviliy edematous, slightly convex, without pro- cases, typical bullous myringitis was seen.” This
nounced deformation, and with traces of a serous study clearly shows that persons with respiratory
liquid in the middle ear cavity.” These authors took tract disease often have ear involvement, including
nasopharyngeal swabs for viral and Mycoplasma MB. Since the ears were not cultured, no conclu-
isolation, performed a paracentesis of each ear- sions can be drawn regarding the role of the Myco-
drum, used a swab to obtain the culture of the plasma.
paracentesis fluid from the external canal, and did
blood serologic studies.
Role of Other Agents
They grew M pneumoniae out of the nasophar-
ynx (NP) of the patient with bullous myringitis, but One case of MB in a 21-year-old man with infec-
not out of the ear drainage. They grew Mpneumo- tious mononucleosis has been reported by Kilpa-
niae from the NP and ear drainage in another trick42; however, cultures were not taken.
patient, and failed to grow it in the third. Feizi et al37 reported a case of a 9-year-old boy
In contrasting their results to that of Rificind et who developed MB while recovering from chicken
al, Sob#{234}slavsk et al mention the differences in ear pox and later developed a generalized severe vesic-
sampling techniques. Whereas Rificind et al did ular eruption similar to that of Stevens-Johnson
direct needle puncture cultures, in Sob#{233}slavsk”s syndrome, although with no eye involvement. He
cases “the swabs were not taken until paracentesis also had serologic evidence ofMpneumoniae infec-
of the eardrum had been made. It seems that this tion.
method gives better chances of isolating the etio- Ruskin43 proposed that MB was caused by latent
logic agent from the affected ear.” vitamin C deficiency and reported that he had
Most investigators agree that a culture of the “successfully treated” ten cases with calcium cevi-
external canal following paracentesis of the ear- tamate injections (into the corpus of his patients,
drum is a poor method of determining what was not their ears).
behind the eardrum originally, since there is con- The above articles document that MB has been
tamination from the external canal’6’20.2329.41 Sob#{232}s- observed in patients with influenza, measles,
lavsk’s own “ear swab” cultures of S albus and S chicken pox, mononucleosis, and unspecified, pre-
aureus suggest that contamination occurred in their sumably viral, URIs, as well as in upper and lower
cases. It is reasonable to speculate that the M respiratory tract M pneumoniae infections.
pneumoniae grown from such a swab was also a
contaminant since the same patient’s NP also grew
SUMMARY
Mpneumoniae, and this same ear sample also grew
“the usual bacterial flora” (whatever that is) along A review of the available English language liter-
with the Mpneumoniae. Other studies have shown ature concerning bullous myringitis (MB) is pre-
the poor correlation between NP flora and cultures sented. The results of needle aspirate cultures for
of middle ear aspirates, making the finding of M M pneumoniae, viruses, and bacteria are summa-
pneumoniae in NP of dubious significance as a rized. The literature associating bullous myringitis
causative agent for otitis.’2 with M pneumoniae and viruses is critically re-
Clyde and Denny,27 in a review of Mycoplasma viewed. In addition, the results of attempts to iso-
infections in childhood, present the case of a 13- late M pneumoniae from cases of (non-MB) otitis
month-old boy with a URI who had a large bullous media are tabulated.
lesion with surrounding erythema on the right tym- In reported culture attempts from cases of bullous
panic membrane. M pneumoniae was recovered myringitis, one of 16 grew Mycoplasma pneumo-
from both the nasophrynx and fluid aspirated from niae, one of 13 a virus, and 43 of 66 bacteria, of
the bullous lesion. They do not report whether which 40 were S pneumoniae, H influenzae or
standard bacterial cultures were done. If this was a hemolytic Streptococcus. Of 858 attempts to isolate
specimen uncontaminated by the external canal, it M pneumoniae from (non-MB) cases of otitis me-
is the only documented case in the literature of MB dia, only one grew M pneumoniae and that was a
with M pneumoniae isolated from the ear itself. If swab from an external canal which was not bacte-
the fluid was bacteriologically sterile, it is the only riologically sterile.
case of a pure culture of M pneumoniae from any The tympanic membrane’s ability to form blisters
middle ear, either with MB or AOM. appears to be a nonspecific reaction. Bullous myrin-
Foy et al reported 1 14 families with an index gitis is merely acute otitis media with blisters within
case of probable primary atypical pneumonia. the substance of the eardrum. There is little evi-
Twelve of their 39 index cases and eight of 59 family dence that otitis media, with or without bullous
cases had “otitis,” which “usually consisted of a myringitis, is caused by Mycoplasma pneumoniae.
congested tympanic membrane, but, in at least two There is bacteriologic data suggesting that bullous

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myringitis should be treated the same as other bacteriology, and management. Pediatrics 49:187, 1972
types of acute otitis media. 24. Tiles JG, Klein JO, Jao RL, et al: Acute otitis media in
children. N Engi J Med 277:613, 1967
25. Rilkind D, Chanock R, Kravetz H, et al: Ear involvement

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The Etiology of Bullous Myringitis and the Role of Mycoplasmas in Ear Disease: A
Review
Donald B. Roberts
Pediatrics 1980;65;761

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 The Etiology of Bullous Myringitis and the Role of Mycoplasmas in Ear Disease: A
Review
Donald B. Roberts
Pediatrics 1980;65;761

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