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					OTITIS MEDIA
1. Definities – terminologie – klassificatie
2. Diagnose
3. Epidemiologie
4. Bacteriologie
5. Pathofysiologie
6. Natuurlijk verloop en therapie
Introduction : the burden of otitis media
• Egyptian mummies have perforations of TM and mastoid
  destruction
• $3.5 billion in expenditures in USA
• Most common reason for visit to pediatrician
• In the developed world AOM is the most common cause
  for prescribing antibiotics in children and accounts for over
  90% of all antimicrobial consumption during the first 2
  years of life (Dagan, 1995).
• Tympanostomy tube placement is 2nd most common
  surgical procedure in children
• Development of multidrug-resistant bacteria
 1. Definition, Terminology, Classification
Otitis media : inflammation of the middle ear without
reference to etiology or pathogenesis
Acute otitis media : inflammation of the middle ear with
rapid onset of one or more local or systemic signs and
symptoms of acute infection within the middle ear (otalgia,
otorrhea, fever, anorexia, vomiting or diarrhea)
Acute otitis media without effusion (myringitis):
erythema and opacification of the eardrum. Blebs or bullae
may be present.
Recurrent otitis media (5 to 10% of children)
   – > 3 episodes of AOM in 3 months with evidence of cure
     between episodes
   – > 4 episodes of AOM in 6 months
Acute otitis media      Normaal TV




   Acute otitis media
Definition, Terminology, Classification
Otitis media with effusion (SOM, OME):
inflammation of middle ear with liquid collected in
middle-ear space. Signs and symptoms of acute
infection are absent; no perforation of the tympanic
membrane
Middle-ear effusion : liquid in middle ear. Effusion
may be serous (thin watery liquid), mucoid (thick
viscid mucus-like liquid), purulent or a combination
of these

An effusion can result from AOM or OME. It can be
of recent onset, acute, or long-lasting, subacute or
chronic.
Otitis media met efusie – secretoire otitis media
glue ear …
Definition, Terminology, Classification

Eustachian Tube dysfunction : middle ear disorder
that can have symptoms similar to those of otitis
media such as hearing loss, otalgia and tinnitus, but
with no middle ear effusion. The dysfunction may be
related to an Eustachian tube that is too closed (i.e.
obstructed) or too open (i.e. patulous).
The latter condition is most frequently associated
with symptoms of autophony.
                 Acute Otitis Media


Resolution       Persistent      Acute Perforation    Suppurative
                 Effusion                +            Complication
                                   Otitis Media


Resolution        Chronic       Resolution    Resolution    CSOM
                   OME              +          Chronic
                                 Healing      Perforation


   Resolution   Sequelae      Perforation No         Recurrent
                                SOM       Otitis      Otitis
                                          Media       Media


                                                             CSOM
                2. Diagnosis
Accurate diagnosis is important to avoid
 unnecessary treatment !
1. Medical history
2. Physical examination
        Diagnosis : Medical history
Otalgia : most common, ear pulling, irritability
Otorrhea
Hearing loss
Fever
Preceding upper respiratory tract infection
Purulent conjunctivitis (Haemophilus influenzae)
Vertigo : not common as a complaint, unilateral disease,
   clumsiness
Nystagmus : labyrinthitis !
Tinnitus
Swelling about the ear : dd mastoiditis, external otitis, adenitis
Facial paralysis
                    Diagnosis
        AOM                        OME
–   preceding URI         –   possible asymptomatic
–   fever                 –   hearing loss
–   otalgia               –   “plugged”
–   otorrhea              –   “popping”
–   hearing loss
 Diagnosis : Physical examination
Adequate examination of the head and neck
 region !
 associated exanthema
 predisposing factors
 alarm symptoms
 …
                    Diagnosis : otoscopy
Tabel: COMPLETES: Mnemonic for Otoscopic Examinations
Color               Gray, white, yellow, amber, pink, red, blue
Other conditions    Fluid level, bubbles, perforation, retraction pocket, atrophic
                    area, otorrhea, bullae, tympanosclerosis, cholesteatoma
Mobility            4+, 3+, 2+, 1+
Position            Neutral, bulging, retracted
Lighting            Battery-charged, halogen or xenon bulb
Entire surface      Visualize all quadrants: ant.superior, post.superior, ant.inferior,
                    post.inferior
Translucency        Translucent or opaque

External auditory   Inflammation, foreign body, displacement, deformed
canal and auricle
Seal                Appropriate-sized speculum
                    Airtight pneumatic system
       3. Epidemiology
Cumulative incidence of otitis media
          Epidemiology : risk factors
I. Host-Related factors (intrinsic)

•   Age
•   gender : males more prone to persistent MEE
•   race : american natives and inuits > whites > blacks
•   cleft palate/craniofacial abnormality/Down Syndrome
•   genetic
•   allergy and immunity
Age

• highest incidence of AOM between 6 months and
  11 months of age
• onset of first episode before 6 months of age is
  strong predictor for recurrent OM
• risk for persistent MEE after AOM inversely
  correlated with age (>4 times when < 2 years of
  age)
Cleft palate/Craniofacial abnormality/Down Syndrome

• OM is present in nearly all infants under 2 years of
  age with unrepaired clefts of the palate
• occurrence reduces following surgical repair
• Children with Down : poor active opening function of
  ET, low resistance of tube
Genetic

• predisposition to recurrent episodes of AOM and
  chronic MEE may have a significant genetic
  component suggested by anatomic, physiologic
  and epidemiologic data
   – twin studies (Norway, Pittsburg)
   – familial clustering
   – genetic markers : G2m(23) associated with rAOM
2. Environmental factors (extrinsic)
•   season and upper respiratory infection
•   day care / home care
•   siblings
•   passive smoking (Etzel et al.)
•   breast feeding / bottle feeding
•   socio-economic status
•   pacifier use
 Relatie seizoen en prevalentie van otitis media
                    WETTEREN
  60

  50

  40                                                      SOM
                                                          < -150
% 30                                                      -50 >< -150
                                                          Normaal
  20                                                      ntb

  10

   0
    okt   nov dec   jan    feb maa   apr   mei   jun
                          maand
                                                 Van Cauwenberge, 1989
    Mean total number of acute RTI diagnosis in
children attending different types of day-care during
     the second and third years of life (N=113)


    1.4 -

    1.2 -                              day-care centre
                                       family day-care
      1-
N                                      home-care
    0.8 -

    0.6 -

    0.4 -

    0.2 -

      0-    |   |   |   |     |    |        |        |
            1   2   3   4    1    2        3        4
OM - smoke exposure

• Induces changes in respiratory tract

• Increased dysfunction of ET, otorrhea,
  chronic and recurrent AOM in children with
  history of parental smoking
             4. Microbiology

• S. pneumoniae – 50-55%
• H. influenzae - 20-25%
• M. catarrhalis - 10-15%
                              }   infernal trio

• Group A strep - 2-4%
• Staph Aureus ?
Infants : higher incidence of gram negative
  bacilli
                              Kweek
Viraal                        48 %    Pitkaranta et al.
                              52%     Galveston et al.

Respiratory syncytial virus
Parainfluenza virus
Influenza virus
Rhinovirus
coronavirus
Chronic MEE

•   previously thought sterile
•   30-50% grow in culture
•   over 75% PCR +
•   usual organisms
  5. Pathogenesis of OM
     Infection           ET dysfunction



             Host respons
 Liberation of inflammatory mediators


    Increase of vascular permeability
     Increase of glandular secretion


Inflammation                Mucosal proliferation
  1. Role of the Eustachian Tube
1. Pressure regulation of
   middle ear
2. Clearance ‘Drainage’ of
   middle ear secretions
  mucociliary
  muscular

3. Protection from sound and
   secretion
  anatomic
  immunologic and mucociliairy
  Developmental Differences between Infants
and Adults in Anatomy of the Eustachian Tube*


• Adults               • Children
  – ant 2/3-             – longer bony portion
    cartilaginous
  – post 1/3- bony
  – 45 degree angle       – 10 degree angle
  – nasopharyngeal        – nasopharyngeal
    orifice 8-9 mm          orifice 4-5 mm in
                            infants
             Eustachian tube

• Usually closed
• Opens during swallowing, yawning, and
  sneezing
• Opening involves cartilaginous portion
• Tensor veli palatini responsible for active
  tubal opening
• No constrictor function
Dysfunction : 1. Impairment of pressure regulation
                     Functional obstruction




                       Open          Weak TVP   Obstruction
                        Anatomic obstruction

     Inflammation               adenoid
                                Tumor




                    Intrinsic                   Extrinsic
                                            After Bluestone
  Dysfunction : 2. Impairment of clearance


• Mucociliary :
- all children with amotile ciliary syndrome
(Kartagener ’s) develop OM
- viral URTI causes destruction of ciliated cells and
therefore predisposes to bacterial OM
• Muscular :
   Animal models : section of TVP & botox, cleft palate
     Dysfunction : 3. Loss of protective function
Anatomic
   • Abnormal patency
   • Short tube
   • Abnormal gas pressures          -
     intratympanic,
     nasopharyngeal           +
   • Non intact middle
     ear-mastoid                             Insufflation

Immunologic
   Secretory system : Mucines, Aquaporins, Cytokines
   Innate immunity
   Infection             ET dysfunction


             Host respons
 Liberation of inflammatory mediators


    Increase of vascular permeability
     Increase of glandular secretion


Inflammation                Mucosal proliferation
  Cumulative acquisition rate of pathogens during
                    first year
100 – %
90 –
80 –                                                    Any pathogen

70 –                                                    M. catarrhalis

60 –                                                    S.pneumoniae
50 –
40 –
                                                        H. influenzae
30 –
20 –
10 –
                                                        Age (months)
          |   |   |   |   |   |   |   |   |   |    |
          1   2   3   4   5   6   7   8   9   10   11   Faden et al., 1997
Cumulative acquisition rates of pathogens
during first year of life
( Faden et al., 1997)

• rapid increase in the first 6 months of life
• 68% of children colonized with 1 or more
  pathogens after 6 months
• colonization rates:
M.cattharalis (55%)>S.pneumoniae (38%) > NTHi (19%)
                           Relationship between frequency of
                           colonization and number of AOM
                            6 –
Episodes of otitis media


                            5 –                                            2

                            4 –        1        3        1    2        1        2
                                                                                      R=0.37
                            3 –        2        4        5        13       4    1
                                                                                      p<0.001
                            2 –        9        13       21       20       13   3

                            1 –        10       19       14       30       6

                            0 –        36       20       19       9        3    1

                                   |        |        |        |        |        |      |
                                  0    1      2      3     4     5    6
                              Frequency of colonization with any pathogen
                                                                                    Faden et al., 1997
Factors affecting colonization rates

• Season
• Number of siblings
• Day care
• Respiratory illness
• Genetic (HLA-A2).(Kalm,1994)
• Immunology
Human Milk Anti-P6 SIgA Antibody Level
                                         700 –
                                             -
                                               -
                                               -                     r=-.26, p=.031
                                               -
                                         600   –
                                               -
                                               -
                                               -
                                               -
                                         500   –
                                               -
                                               -
                                               -
                                               -
                                         400   –
                                               -
                                               -
                                               -
                                               -
                                         300   –
                                               -
                                               -
                                               -
                                               -
                                         200   –
                                               -
                                               -
                                               -
                                               -
                                         100   –
                                               -
                                               -
                                               -
                                               -
                                           0         |     |     |          |         |
                                                     0     1     2          3         OP
                                                   Episodes of Otitis Media
Pathofysiology (1): Development of otitis
media

• Pathogens must adhere to nasopharyngeal
epithelium
• Pathogens must enter the ME cavity through the
Eustachian tube (ET)
• Pathogens must be able to withstand and overcome
the defensive mechanisms of tubotympanum
• Viruses, IgE-mediated hypersensitivity , overuse
(inadequate) use of antibiotics, may trigger changes
in nasopharyngeal flora leading to otitis media.
Pathofysiology (2) : Development of otitis media


• The normal tubotympanum is protected by the
mucociliary system and the secreted molecules of innate
immunity.
• During infections, these systems provide the critical first
line of defense before the activation of adaptive immunity
•The development of specific mucosal immunity against
these bacteria may be under genetic control.
Pathofysiology (3) : Development of otitis media

• There are many reasons why the Eustachius tube
may be dysfunctional. The clinician should
determine the most likely etiology to direct
management decisions.
• Since there is now evidence that upper
respiratory tract infections can precede an episode
of either acute otitis media or otitis media with
effusion, management should be focused of
prevention of these viral infections
                 6. Treatment


6.1 Treatment Acute otitis media
Goals:
• Decreasing the duration of fever and pain
• Expediting the resumption of normal
  activity
• Limiting the small potential for suppurative
  complications
• Spontaneous cure in up to 80 percent of
  children treated only with analgesics
• Antibiotics increase cure rate to 94 percent,
  and decrease duration of symptoms and risk
  of complications
• Broad spectrum antibiotics probably offer
  no advantages over standard antimicrobials
                Take into account:

• History of allergy or intolerance to a
  particular antibiotic or class of antibiotic
• Presumed causative organism
  (Streptococcus pneumoniae is most likely in
  a child previously untreated for AOM)
                Take into account:

• Antibiotic exposure within the previous 30
  days may have caused resistant organisms
  to predominate
• Conjunctivitis/Otitis Syndrome is
  suggestive of H. influenzae infection
Worldwide view of resistance to S.pneumoniae




                                  Steele RW, 1995
    Evolution of penicillin-resistance (I + R, %)
      in pneumococci for common infections
             (1989 - 2000) in Belgium

                            Penicillin
        18
        16
        14
        12
    % R 10
         8
         6
         4
         2
         0
              1989   1991   1993    1995   1997   1999

Verhaegen et al.
Problem of Resistance

   • Strep. Pneumoniae
      – Target resistance
   • H. influenzae and M. catarrhalis
      – beta-lactamase production
      – All M. catarrhalis +
      – 15-25% of H. influenzae
      Clavulanic acid
Blinde start (empirische therapie) of
     na (kweek) antibiogram ?
• « Blind »
  – Vooral in routine, ongecompliceerde infectie,
    goed gedocumenteerd in (rec) literatuur
• Op basis va kweek/antibiogram
  – Vooral indien ernstig, herhaaldelijk, mislukking
    (verwekker/antibiogram onvoorspelbaar)
Follow-up

• Once antibiotic treatment is initiated the child
  should demonstrate symptomatic benefit within 72
  hours
• Failure to show improvement indicates need for
  re-evaluation.
• A follow-up examination should be scheduled for
  one month after the diagnosis and should include:
      - Inspection of the tympanic membrane
      - Assessment of hearing
Follow-up

• The purpose of the follow-up exam is to identify
  persistent otitis media or persistent middle ear
  effusion
• Children with persistent otitis media or persistent
  middle ear effusion should be seen on a monthly
  basis until their exam is normal
6.2 Treatment Recurrent Otitis media

• Chemoprophylaxis
  – Sulfisoxazole, amoxicillin, ampicillin
  – less efficacy for intermittent propylaxis
• Myringotomy and tube insertion
  – Decreased frequency and severity of AOM
  – otorrhea and other complications
  – may require prophylaxis if severe
• Adenoidectomy
  – 28% and 35% fewer episodes of AOM at first and
    second years
6.3 Treatment Recurrent Otitis media

Spontaneous resolution rates for OME
OME persisting after AOM    1m       60%   (55-65%)
                            3m       74%   (67-80%)
OME of unspecified duration <1m      52%   (47-58%)
                            2-3m     63%   (60-66%)
                            4-6m     76%   (73-79%)
                            7-9m     82%   (79-86%)
                            10-12m   88%   (84-90%)
                            13-15m   92%   (89-95%)
                            16-24m   97%   (95-99%)
 Natural history of OME


• Extremely dynamic course of OME :
  30-40% of children have recurrent episodes
• Spontaneous resolution depending on seasonal
  variation
• Seasonal trends < important in long-term cases
Natural history of OME


1. Most OME resolves within a few months,
  prognosis inversely related to duration : newly
  diagnosed OME does extremely well, OME
  lasting weeks or months does poorly
2. The chance of spontaneous resolution diminishes
  greatly after 3-6 months
 Medical therapy
1. Antibiotic therapy of OME has a modest impact
  on short-term resolution
2. The impact on long-term resolution is smaller,
  if not negligible (Mandel, Giebink)
3. Steroid therapy and antihistamine-decongestant
  therapy have no proven effect on resolution of
  OME
Surgical therapy
• Ventilation tubes
• Adenoidectomy

Maw, 1993
•   Beneficial effect of tubes or adenoidectomy compared with no surgery
•   Further improvement when combination of tubes and adenoidectomy

Gates, 1987
After adenoidectomy
•         significant less time with effusion
•         longer time to first recurrence
•         fewer surgical re-treatments
• No surgery (n=77)                                     100
• Ventilation tube only




                          Proportion (%) with fluid remaining
   (n=77)                                               90
• Adenoidectomy only
• Adenoidectomy                                                 80
   and tube (n=136)
                                                                70
                                                                60
                                                                50
                                                                40
 Survival                                                       30
 functions                                                      20
 for time to
                                                                10
 fluid Clearance
                                                                0                  Years
 as Confirmed
 by otoscopy                                                         0   1   2   3 4   5 6   7    8   9 10
                                                                                             Maw et al, 1994
       Tympanostomy tube insertion
• Unresponsive OME >3 months bilaterally, or > 6
  months unilateral, sooner if associated hearing
  problems
• Recurrent MEE with excessive cumulative
  duration
• Speech – language delay
• Recurrent AOM - >3/6 monthss or >4/12 months
• Eustachian tube dysfunction
• Suppurative complication
• Severe tympanic membrane retraction
Inconveniences of ventilating tubes

o short general anaesthesia
o ‘open’ middle ear
o atrophy and atelectasis of tympanic membrane
o surgical complications
Negative Prognostic factors

•   Passive smoking
•   Younger children at onset of OME
•   Craniofacial malformations, Down syndrome
•   Day-care attendance
              Otitis media
klinische   directe en indirecte   antibioticum
gevolgen          kosten            resistentie




                  PREVENTIE
              Preventie OMA
• Beïnvloeden risicofactoren

• Chirurgie

• Chemoprofylaxie

• Immunoprofylaxie
1. Beïnvloeden risicofactoren
• Gastheer   afwijkingen KNO-gebied
             immunologische afwijkingen


• Omgeving   dagverblijf
             passief roken
             fopspeen

             borstvoeding beschermt
2. Chemoprofylaxie


• Meta-analyse (9 studies)

• Antibioticum profylaxie        0.11 episodes
  OMA / maand



                         Williams et al. JAMA 1993
                                 Antibioticaprofylaxie
                                     Grafiek profylaxis
                          50 –                                             S.pneumo
                                 Prophylaxis 4-6 mo
                          40 –
% with resistant strain




                                                                             H.flu

                                                                            M.cat
                          30 –

                          20 –

                          10 –

                           0–|   |     |   |   |      |   |   |    |   |
                             0   1     2   3   4   5      6   7   8    9
                                               Month
                                                              Brook CID 1996
                                Chemoprofylaxie met
                                     Xilitol

Cumulative incidence of AOM                        Cumulative incidence of AOM
 0.6 -
                                                   0.3 -
 0.5 -
 0.4 -
                                                   0.2 -
 0.3 -
                                                                                           Control
 0.2 -                                   control   0.1 -                                   Xylitol
                                         Xylitol                                           Lozenge
 0.1 -
   0                                                 0
       1   15   30   45   60   75   90                   1   15   30   45   60   75   90

                 Time (days)                                       Time (days)


   Xilitol syrup                                      Xilitol chewing gum/lozenge




                                                   Uhari et al. Pediatrics 1998
3. Immuunprofylaxie

~ Microbiologie

• Passieve immuunprofylaxie
  (immuunglobuline)

• Actieve immuunprofylaxie
  (vaccinatie)
3.1. Passieve immuunprofylaxie

Gammaglobuline IV   - OM model in chinchilla’s
                    (Shurin et al. 1988)

                    - kinderen met rec. OMA
                     (Shurin et al.1993)
RSV IG IV           - reduce incidence and severity of
                      RSV lower respiratory tract
                      infections
                      (Simoes et al. 1996)
 3.2.Actieve immuunprofylaxie
 (vaccinatie)
Influenza A virus vaccin

Finland
Kinderen 1-3 jaar
Follow-up 6 weken

Aan influenza A virus gerelateerd aantal OMA     86%
Totaal aantal OMA (in influenzae seizoen) :      36%

                  Heikinen et al. Am J Dis Child 1991
Pneumococcen vaccins

• Pneumococcen polysaccharide vaccin
  ( Pneumovax / Pneumune)

• Pneumococcen conjugaatvaccin
  ( Prevenar)
                       Vaccine efficacy on AOM prevention
                    Belgian OMAVAX trial                                            Dutch OMAVAX trial

                                              PCV/PSV
                                                                                                        PCV/PSV
Cumulative hazard




                                                            Cumulative hazard
                                               Control


                                                                                                             Control




                          n = 78                                                       n = 383
                          RR (95% CI): 1,16 (0,69 – 1,96)                              RR (95% CI): 1,29 (1,02 – 1,62)
                                                                                       10



                    Time after complete vaccination                              Time after complete vaccination

                                 Dhooge & Van Kempen, 2002                      Veenhoven et al, abstract ISPPD, 2002

				
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