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REV LARYNGOL OTOL RHINOL.

2004;125,3:165-169. O T O L O G Y
THERAPEUTIC NOTE

Traitement de la mastodite aigue :


propos de 31 cas sur une priode de 10 ans A. Mustafa 1
Ch. Debry 2
M. Wiorowski 2
Treatment of acute mastoiditis: E. Martin 2
A. Gentine 2
Report of 31 cases over a ten year period (Prishtina, Strasbourg)

Rsum Summary
Objectif : Avec la possibilit de complications extra et Objective: With possible extracranial and intracranial
intra-crniennes, la mastodite aigue est la principale complications, acute mastoiditis is the leading complication of
complication des otites moyennes aigues (OMA). Le but de acute otitis media (AOM). The goal of this study is to assess the
cette tude est d'valuer les signes cliniques, les germes clinical features, pathogens, complications and especially
pathognes, les complications et particulirement la gestion des management of acute mastoiditis in the ENT service, University
mastodites aigues dans le service ORL de lHpital Hospital of Strasbourg, France. Methods: Systematic review of
Universitaire de Strasbourg, France. Mthodes : tude all medical records of patients who were admitted with acute
rtrospective de tous les dossiers mdicaux des patients qui ont mastoiditis from January 1993 to April 2003. Results:
t admis pour une mastodite aigue de janvier 1993 avril 31 patients, 18 male (58%) and 13 female (42%) fulfilled
2003. Rsultats : 31 patients, 18 de sexe masculins (58 %) et inclusion criteria. The average age was 16, going from
13 de sexe fminins (42 %) ont remplis les critres d'inclusion. 6 months to 70 years, with 55% between 0 to 5 years. Most
L'ge moyen tait de 16 ans (6 mois 70 ans), avec 55 % entre common symptom was otalgia (84%), 58% of patients had
0 et 5 ans. Les symptmes les plus communs taient l'otalgie history of past AOM and 61% were under antibiotic therapy
(84 %), un antcdent dOMA (58 %) et 61 % taient sous during admission. Twenty-three patients (74%) presented retro-
antibiothrapie lors de l'admission. Vingt-trois patients (74 %) auricular swelling and erythema. 18 (58%) had a displaced
ont prsent un oedme et un rythme rtro auriculaire. pinna. Cultures taken from pus isolated Streptococcus pneumo-
18 (58 %) ont eu un pavillon dcoll. Les cultures des niae in 12 cases (38.7%), Pseudomonas aeruginosa in 2 cases
prlvements de pus ont isol le streptocoque pneumoniae dans (6.4%), Streptococcus beta-haemolyticus 1 case, Staphylo-
12 cas (38.7 %), le pseudomonas aeruginosa dans 2 cas coccus coagulase-positive 1 case and Mycobacterium tubercu-
(6.4 %), le streptocoque bta-hmolytique 1 cas, un cas de losis hominis 1 case (3%). Complications of acute mastoiditis
staphylocoque coagulase positive et 1 cas de tuberculose de occurred in 3 cases (10%): Meningitis 2 cases and facial nerve
mycobactrie tuberculeuse hominis (3 %). Les complications paralysis 1 case. Surgery therapy was performed in 84% of
des mastodites aigues se sont produites dans 3 cas (10 %) : cases (mastoidectomy only or in combination with myringotomy
2 mningites et 1 paralysie du nerf facial. La chirurgie a t with tube insertion) and medical therapy only in 16% of cases.
effectue dans 84 % des cas (mastoidectomie seule ou associe Conclusion: Despite use of antibiotics, acute mastoiditis
une paracentse avec mise en place dun arateur trans remains still a threat for patients with AOM, especially for
tympanique) et le traitement mdical seul dans 16 % des cas. children under 5 years of age. Great care is required from
Conclusion : En dpit de l'utilisation des antibiotiques, la clinicians to make an early diagnosis in order to promote
mastodite aigue reste toujours une menace pour des patients adequate management and prevent complications.
avec AOM, particulirement pour les enfants au-dessous de
5 ans. Le plus grand soin doit tre apport par le clinicien pour
faire un diagnostic prcoce afin de mettre en place un traite-
ment adapt et ainsi dviter la survenue de complication.

Mots-cls : Mastodite aigue, otite moyenne aigue, traitement mdical, Key-words: Acute mastoiditis, acute otitis media, medical treatment,
mastodectomie, paracentse. mastoidectomy, myringotomy.

INTRODUCTION
1. University Clinical Centre, ENT-Head and Neck Surgery Clinic,
Prishtina, Kosovo, UNMIK.E-mail: aziz_mustafa2000@yahoo.com Acute mastoiditis is an acute inflammatory disease
2. Strasbourg University Hospital, Hautepierre Hospital, ENT-Head & of the mastoid process. Mastoiditis is usually a bacterial
Neck Surgery Department, Avenue Moliere 1, F-67098 Strasbourg infection and its incidence has declined since the intro-
cedex, France.
duction of antibiotics. During the 1950s 0.4% of acute
Article received: 07/07/03 accepted: 08/06/03

Treatment of acute mastoiditis: Report of 31 cases over a ten year period, A. Mustafa, Ch. Debry, M. Wiorowski et al. 165
episodes of acute otitis media (AOM) developed into TABLE II: Distribution by age.
acute mastoiditis, whereas the reported incidence during
the 1980s was 0.004% (1). Age (years) Patients
As the transition of otitis media to acute mastoiditis 0-1 5
decreased with use of antibiotics, the incidence of extra- 2-5 12
temporal complications also decreased from 2.3% to 6-10 0
0.24%, (2, 3). Regardless of this optimistic trend, in 11-20 7
recent years sporadic reports have described possible 21-30 1
resurgences of acute mastoiditis (4). 31-40 1
41-50 1
The goal of this study was to assess the incidence of 51-60 1
acute mastoiditis, development of complications, their 61-70 3
clinical features, bacteriologic diagnostic and therapeutic
procedures in ENT Service of Hautpierre University
Hospital in Strasbourg, France, between 1993 and 2003. (12 patients) (Table II). The average age was 16. Concer-
ning age, our series is divided in two groups:
PATIENTS AND METHODS
Group I: under the age of 5 - 17 patients and,
The clinical records of patients admitted with the
Group II: above the age of 11 14 patients.
diagnosis of acute mastoiditis and treated at ENT-Head
and Neck Surgery Department, Hautepierre University There were no patients in the group from 6 to
Hospital in Strasbourg, France from January 1993 to 10 years old.
April 2003, were reviewed.
History, physical examination, CRP and WBC are
The diagnosis of acute mastoiditis was established recorded in table III. The most common symptom is
by experienced otolaryngologists based on the demons- otalgia (83.87% of cases), 58% of them had history of
tration of otitis media or pus in the middle ear, by myrin- AOM and 61% were under antibiotic therapy at the
gotomy combined with one or more of the following moment of admission. Typical signs (retroauricular
physical signs, post auricular swelling, erythema and swelling and erythema) were present in 74.19% of cases.
displaced pinna. CRP was elevated in 48.38% of cases, whereas the WBC
above 15 was only in 29% of cases. There were no
The demographic data included the sex and age.
significant differences between two groups of age
Signs and symptoms on admission, white blood count
(<5 years old, >11 years old) concerning history,
(WBC), C-reactive protein (CRP) results and middle ear
physical examinations and laboratory results.
aspirate culture performed on admission were also
recorded. Imaging studies, x-rays of mastoid, CT and In 24 cases in which pus was harvested either by
MRI of mastoid were done in all cases with a suspected myringotomy or in open surgical exploration, it was
complication. Medical and surgical therapies were
recorded. All cases of complications and their treatment TABLE III: Clinical history and laboratory results on
were noted. admission of 31 patients with acute mastoiditis.
Feature Nr. of patients (%)
TABLE I: Distribution by sex.
History
Male 18 (58.06%) Otalgia 26 (83.87%)
Female 13 (41.93%) Fever (> 38C) 15 (48.38%)
Otorrhea 8 (25.80%)
Total 31 (100%) Upper resp. tract infection 8 (25.80%)
AOM in the past 18 (58.06%)
AOM in the last week 17 (54.83%)
RESULTS Antibiotic treat. in the last week 19 (61.29%)
During the 10-years period, from January 1993 to Physical examination
April 2003, established inclusion criteria fulfilled Retro-auricular swelling 23 (74.19%)
31 clinical records. 18 patients (58%) were male and Retro-auricular erythema 23 (74.19%)
13 (42%) were female (Table I). Displaced pinna 18 (58.06%)
More than one sign 23 (74.19%)
We found also no change in the annual incidence of Laboratory results
the acute mastoiditis during the 10 years of the study.
CRP (more than 10) 15 (48.38%)
Patients are aged from 6 months to 70 years, with Leucocytosis (>15 x1.000.000.000/L) 9 (29.03%)
predominance of age 0-1 year (5 patients) and 2-5 year AOM - acute otitis media CRP- C reactive protein

166 REV LARYNGOL OTOL RHINOL. 2004;125,3:165-169.


TABLE IV: Bacteriologic results of cultures. tomy, for the second group most often method of
treatment is simple mastoidectomy and medical therapy
Microorganism Group I Group II Total (Table VI).
<5 years > 11 years The type of antibiotics used for treatment of acute
mastoiditis with or without surgery are shown in
Streptococcus pneumoniae 9 (29.03%) 3 (9.67%) 12 (38.70%)
Pseudomonas auriginosa 1 (3.22%) 1 (3.22%) 2 (6.45% ) table VII.
Streptococcus beta-haemolyticus 1 (3.22%) 0 1 (3.22%)
Staphylococcus coagulase-positive 0 1 (3.22%) 1 (3.22%) TABLE VII: Antibiotics (by antibiogram) used for treat-
Mycobacterium tuberculosis hominis 0 1 (3.22%) 1 (3.22%)
ment of acute mastoiditis.
Sterile 3 (9.67%) 4 (12.9%) 7 (22.36%)
Not taken material 3 (9.67%) 4 (12.9%) 7 (22.36%) Type of antibiotic Nr. of patients %
Total 31 (100%)
amoxicilline + clavulonic acid 13 42%
ceftriaxone 4 13%
cultured in a laboratory. Micro-organisms were identified cefriaxone + metronidazole 2 6.45%
for 17 patients: Streptococcus pneumoniae (n=12), ofloxacine 2 6.45%
Pseudomonas aeruginosa (n=2), Streptococcus beta- cefotaxime 2 6.45%
cefotaxime + metronidazole 1 3.22%
haemolyticus (n=1), Staphylococcus coagulase-positive
cefotaxime + vancomycine 1 3.22%
(n=1) and Mycobacterium tuberculosis hominis (n=1). cefotaxime + amikacine 1 3.22%
7 cultures remained sterile. In 7 cases bacteriologic amoxicilline 1 3.22%
analysis was not done. There was significant difference cefuroxime 1 3.22%
in bacteriology results between two groups of patients: ciprofloxacine + metronidazole 1 3.22%
Streptococcus pneumoniae is frequent in the group under ceftazidine + metronidazole 1 3.22%
5 years old (Table IV). tuberculostatics
(izoniazide + rifampicine + ethambutole) 1 3.22%
In our series, for 31 cases with acute mastoiditis we
find 3 cases (9.67%) of complications (Table V). All Total 31 100%
cases are treated and healed without sequelae after long
The dose was standard for each antibiotic, the way of
follow-up.
administration was intravenous and the duration of
therapy was 2-7 days, followed by a 10 days oral
TABLE V: Complications of acute mastoiditis. administration as outpatient. One patient with tuber-
Complications Nr. culous mastoiditis underwent tuberculostatic therapy for
6 months.
Facial nerve paralysis 1
Meningitis 2 DISCUSSION
Total 3 Acute mastoiditis is the most common complication
of acute otitis media (AOM), and may be the first clinical
Treatment of acute mastoiditis in our series was
sign of a middle ear infection, especially for young
medical only in 5 cases (16.12%) and surgical in combi-
children (4-6). Lack of a well-developed immune system
nation with antibiotics in 26 cases (83.81%). Surgery
and difficulties in diagnosing AOM, can account for part
went from myringotomy with ventilation tubes insertion
of the rise in the incidence of complications of purulent
to mastoidectomy with or without myringotomy and
middle ear infections for children. Antibiotic treatment of
surgery for complications. There are also significant
AOM is certainly not an absolute safeguard against
differences between two groups of age concerning
development of complications. Antibiotic therapy may
therapy of acute mastoiditis: most often method of treat-
have a masking effect on significant signs and symptoms
ment in the first group is mastoidectomy with myringo-
of complications, causing delay in diagnosis (1, 3, 7).
In industrialized countries, the estimated incidence
TABLE VI: Treatment of acute mastoiditis. of acute mastoiditis is 2-4 out of 100 000 AOM (8).
Group I Group II However, complications have not changed in number and
Method of treatment Total
<5 years > 11 years severity and they mainly include; subperiostal abscess,
labyrinthtis, facial nerve paralysis, meningitis, cerebral
Medical treatment only 1(3.22%) 4 (12.9%) 5 (16.12%)
Myringotomy and ventilation abscess, lateral sinus thrombosis and death (9). In our
tube insertion 4 (12.9%) 0 4 (12.90%) study we find 31 cases of acute mastoiditis as complica-
Simple mastoidectomy 3 (9.67%) 6 (19.35%) 9 (29.03%) tion of AOM or CSOM on the period of 10 years. Com-
Mastoidectomy and myringotomy 9 (29.03%) 2 (6.45%) 11 (35.48%) plications of acute mastoiditis are very uncommon in
Surgery for complications 0 2 (6.45%) 2 (6,45 %) developed countries. We find 3 cases of complications of
Total 31 (100%) acute mastoiditis over a 10-year period.

Treatment of acute mastoiditis: Report of 31 cases over a ten year period, A. Mustafa, Ch. Debry, M. Wiorowski et al. 167
The average age of patients in some of the series was 48%. About 58% of the patients had episode of AOM in
5.3 years (1), 5.5 years (3), 4 years and 7 months (4), the past, 55% in the last week. Retroauricular swelling
11 years and 2 months (5), 4 years (6) and 17 months and erythema were seen in 75% of cases, whereas
(10) for children population. In our series including displaced pinna were present in 58.06% percent of cases.
children and adults, the average age was 16. For this CRP was elevated in 48% of cases; WBC greater than 15
purpose, we divided the studied population in two million per litre was in 29% of cases.
groups: the first group, under the age of 5, 17 patients
Despite a wide use of antibiotics, in the latest years a
(55%) and the second group, above the age of 11,
rise in the incidence of complications of AOM has been
14 patients (45%) and we analysed differences in history,
mentioned in literature (1, 3, 4, 7, 14, 15). There are also
examination, laboratory, microbiology results and methods
reports of more than one complication for the same
of treatment.
patient. From 124 patients (5 months-16 years of age),
Microbiological results of specimens taken from the 9% developed endocranial complications: Lateral sinus
middle ear and mastoid show that the most common thrombosis (n=5), meningitis (n=5), epidural abscess
isolated microorganism is Streptococcus pneumoniae in (n=5), one cerebral and one cerebellar abscess, 4 develo-
23%, group A Streptococcus in 16%, coagulase-staphylo- ped more than one complication at the same time (14).
coccus in 19%, Staphylococcus aureus in 5% and Intracranial and extracranial complications for the same
Haemophilus influenzae in 2% of the cases. No growth patient can occur, as for example Bezolds abscess with
occurred in 20% of all cases (7, 11). In another study multiple dural sinus thromboses (16). In a large series of
(28 cases), cultures show growth in 16 cases (57%); 2890 cases of chronic otitis media (COM) there were
Streptococcus pneumoniae was present in 8 cases 93 (3.22%) with complications: 57 (2%) intracranial and
(28.6%), Staphylococcus aureus in 10 cases (37%) and 39 (1.35%) extracranial. For 3 patients more than one
one case of Haemophilus, one of Proteus mirabilis and complication was observed (15). In our study, 3 patients
one of Eschecheria coli (3.6%) (8). Some studies suggest have complications: Meningitis (n=2) and facial nerve
that Pseudomonas auriginosa is the leading pathogen paralysis (n=1). There was no more then one complica-
isolated from acute mastoiditis cultures (1, 12). In our tion for the same patient for this period. All 3 cases with
study we get the following bacteriologic results: complications were promptly treated: One patient with
Streptococcus pneumoniae was found in 12 out of meningitis in group I treated with medical therapy only,
31 cases (38.7%), Pseudomonas auriginosa in 2 cases 2 cases in the group II, one meningitis and one facial
(6.45%), and Streptococcus beta-haemolyticus, Staphylo- nerve paralysis treated with medical and surgical therapy.
coccus coagulase-positive and Mycobacterium tubercu- All healed without sequelae and no recurrence was noted
losis hominis each in one case (3%). About 22% of during the follow-up.
cultures remained sterile and 22% of bacteriology exam
Acute mastoiditis can be treated successfully with a
were not undertaken. In the group of children under
broad spectrum of intravenous antibiotics and myringo-
5 years, Streptococcus pneumoniae is isolated in about
tomy. Dooghe et al reported a mastoidectomy in 25% of
30% of all cases. In the group of adults and children
the cases although 65% received only a medical treat-
above 11 years, Streptococcus pneumoniae is isolated in
ment. In theses cases, no further treatment was required
about 10% of all cases.
and no recurrence was observed (7). Tarantino et al
Acute mastoiditis occurs for young children, and in performed a myringotomy in 20% of the cases, a
the majority of these without a previous history of acute mastoidectomy in 12.5% of the cases and an antro-
otitis media. While acute mastoiditis for children was atticotomy in 2.5% (8). Current literature supports the
associated to otalgia, fever, tympanic membrane treatment of uncomplicated acute mastoiditis with
abnormality and auricular displacement, increased WBC myringotomy and intravenous antibiotic therapy (17). A
counts and CRP results in addition to prolonged symp- majority authors agree that elevated WBC counts, fever
tom duration, were predictors for subsequent mastoidec- and retroauricular displacement during hospitalization
tomy (13). Otalgia, often manifested as irritability, was are important factors for subsequent mastoidectomy (13).
the most frequent symptom (80%), followed by fever One must maintain a high index of suspicion for an
(50 %), poor feeding (40%) and vomiting (15%). Upper intracranial complication of acute mastoiditis for the
respiratory tract infection was present in 60% of cases. In patients who have been previously on oral antibiotics for
75% of them we observed postauricular swelling (with otitis media and have atypical or prolonged presenting
erythema, disappearance of the auricular sulcus and signs and symptoms (3). In our study, the most common
proptosis of the auricle). The remaining 25% also had therapy was mastoidectomy with myringotomy in 35.5%
postauricular fluctuation (8). In almost half (48%), the of the cases as reported in table VI. Although we have
episode of acute mastoiditis was the first recognized found some differences in the management of the two
evidence of pathologic conditions of the ear. Fifty-six groups of age (table VI), as the samples are too small it is
percent of patients were taking oral antibiotics prescribed not possible to make some statistical analysis. The most
by their primary care physician within the 12 days before often used antibiotics were amoxicilline + clavulonic
admission (4). In our study, the most common symptom acid in 13 cases (42%) and cefriaxone 4 cases (13%). We
of ear disease was otalgia (84%). Fever was present in found differences in the therapy between two groups of
168 REV LARYNGOL OTOL RHINOL. 2004;125,3:165-169.
age. On 17 patients under age of 5 years, 9 (30%) 4. SPRATLEY J, SILVEIRA H, ALVAREZ I, PAIS-CLEMENTE M.
Acute mastoiditis in children: Review of the current status. INT J
underwent mastoidectomy with myringotomy, 4 (13%) PEDIATR OTORHINOLARYNGOL. 2000 Nov 30;56(1):33-40.
myringotomy with ventilation tube insertion, 3 (10%) 5. LINDER TE, BRINER HR, BISCHOF T. Prevention of acute
simple mastoidectomy and only 1 (3%) medical therapy mastoiditis: Fact of fiction? INT J PEDIATR OTORHINOLARYNGOL.
only. On 14 patients in the second group, 6 (20%) were 2000 Nov30;56(1):129-34.
treated with simple mastoidectomy, 4 (13%) with 6. GHAFAR FA, WORDEMANN M, MCCRACKEN G. Acute
mastoiditis: A seventeen-year experience in Dallas, Texas. PED INF
medical therapy only, 2 (6.45%) with mastoidectomy and DIS J. 2001 Apr;20(4):376-80.
myringotomy and 2 (6.45%) with surgery for complica- 7. DHOOGE IJM, ALBERS FWJ, VAN CAUWENBERGE PB.
tion (mastoidectomy with atticoantrotomy). Intratemporal and intracranial complications of acute suppurative
otitis media in children: Renewed interest. I NT J P EDIATR
We didnt find any difference in the therapy of acute OTORHINOLARYNGOL. 1999 Oct;49(Suppl.1):S-109-111.
mastoiditis in comparison with the period 1993-1997 and 8. TARANTINO V, D`AGOSTINO R, TABORRELLI G,
1998 and 2003, which could indicate an evolution of the MELAGRANA A, PORCU A, STURA M. Acute mastoiditis:
treatment of this pathology in our department. A 10 year retrospective study. INT J PEDIATR OTORHINOLARYNGOL.
2002 Nov11;66(2):143-8.
In our series, all cases with acute mastoiditis recove- 9. VERA-CRUZ P, FARINHA RR, CALADO V. Acute mastoiditis in
red without sequelae and no recurrent disease was children our experience. INT J PEDIATR OTORHINOLARYNGOL.
1999;50:113-117.
recorded during long-time follow-up.
10. FRANOIS M, VAN DEN ABBEELE T, VIALA P, NARCY P.
Mastoidites aigues extriorises de lenfant: propos dune srie
CONCLUSION de 48 cas. ARCHIVES DE PEDIATRIE. 2001 Oct;8(10):1050-54.
11. ZAPALAC JS, BILLINGS KR, SCHWADE ND, ROLAND PS.
Despite use of antibiotics, acute mastoiditis still Suppurative complications of acute otitis media in the era of
remains a threat for patients with AOM, especially for antibiotic resistance. ARCH OTOLARYNGOL HEAD NECK SURG. 2002
children under 5. Great care is required by clinicians to Jun;128(6):660-3.
reach an early diagnosis in order to promote adequate 12. BUTBUL-AVIEL Y, MIRON D, HALEVY R, KOREN A,
SAKRAN W. Acute mastoiditis in children: Pseudomonas
management and prevent complications. aeruginosa as leading pathogen. I NT J P EDIATR O TORHINO
LARYNGOL. 2003 Mar;67(3):277-81.
Literature 13. KVESTAD E, KVAERNER KJ, MAIR IW. Acute mastoiditis:
Predictors for surgery. INT J PEDIATR OTORHINOLARYNGOL. 2000
1. LUNTZ M, BRODSKY A, NUSEN S, KRONENBERG J, KEREN Apr15;52(2):149-55.
G, MIGIROV L, COHEN D, ZOHAR S, SHAPIRA A, OPHIR D, 14. SCHWARGER K, CARDUCCI F. Endocranial complications of
FISHMAN G, KISILEVSKY V, MAGAMSE I, ZAAROURA S, acute and chronic otitis media in children and adolescents.
JOACHIMS HZ, GOLDENBERG D. Acute mastoiditis the LARYNGORHINOOTOLOGIE. 1997 Jun;76(6):335-40.
antibiotic era: A multicenter study. I NT J P EDIATR O TORHINO
LARYNGOL. 2001 Jan;57(1):1-9. 15. OSMA U, CUREOGLU S, HOSOGLU S. The complications of
otitis media: Report of 93 cases. J L ARYNGOL O TOL . 2000
2. KANGSANARAK J, NAVACHOROCHEN N, FOOANANT S, Feb;114(2):97-100
RUCKPHAOPUNT K. Intracranial complications of suppurative
otitis media: 13 years experience. AM J OTOL. 1995 Jan;16(1):104- 16. ZAPANTA PE, CHI DH, RUSELL AF. A unique case of Bezolds
9. abscess associated with multiple dural sinus thromboses.
LARYNGOSCOPE. 2001 Nov;111:1944-48.
3. GO C, BERNSTEIN JM, DE JONG AL, SULEK M, FRIEDMAN
EM. Intracranial complications of acute mastoiditis. INT J PEDIATR 17. BAUER PW, BROWN KR, JONES DT. Mastoid subperiostal
OTORHINOLARYNGOL. 2000 Apr15;52(2):143-8. abscess management in children. I NT J P EDIATR O TORHINO
LARYNGOL. 2002 May;63(3):185-8.

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