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 Effusion

Acute Perforation + Otitis Media

Resolution + Healing

Suppurative Complication

Resolution

Chronic OME

Resolution Chronic Perforation

CSOM

Resolution

Sequelae

Perforation No Otitis SOM Media

Recurrent Otitis 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
preceding URI fever otalgia otorrhea hearing loss

OME
possible asymptomatic hearing loss plugged popping

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 Other conditions Mobility Position Lighting Entire surface Translucency Gray, white, yellow, amber, pink, red, blue Fluid level, bubbles, perforation, retraction pocket, atrophic area, otorrhea, bullae, tympanosclerosis, cholesteatoma 4+, 3+, 2+, 1+ Neutral, bulging, retracted Battery-charged, halogen or xenon bulb Visualize all quadrants: ant.superior, post.superior, ant.inferior, post.inferior Translucent or opaque

External auditory canal and auricle Seal

Inflammation, foreign body, displacement, deformed 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 -50 >< -150 Normaal 20 ntb

% 30

10
0 okt

nov dec

jan

feb maa maand

apr

mei

jun 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 1day-care centre family day-care home-care

0.8 0.6 0.4 0.2 -

0-

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% infernal trio M. catarrhalis - 10-15% Group A strep - 2-4% Staph Aureus ? Infants : higher incidence of gram negative bacilli

Viraal

Kweek 48 % 52%

Pitkaranta et al. 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 ant 2/3cartilaginous post 1/3- bony 45 degree angle nasopharyngeal orifice 8-9 mm Children longer bony portion

10 degree angle nasopharyngeal 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 Insufflation ear-mastoid

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

100 % 90 80

Cumulative acquisition rate of pathogens during first year

Any pathogen
M. catarrhalis S.pneumoniae

70
60 50

40
30 20
H. influenzae

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

2 1 2 9 10 36 | | 3 4 13 19 20 | 1 5 21 14 19 | 2 13 20 30 9 | 1 4 13 6 3 1 | | 2 1 3

4
3 2 1 0

R=0.37 p<0.001

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

700 600 500 400 300 200 100 0

r=-.26, p=.031

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
Verhaegen et al.

1991

1993

1995

1997

1999

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

Proportion (%) with fluid remaining

No surgery (n=77) Ventilation tube only (n=77) Adenoidectomy only Adenoidectomy and tube (n=136)

100 90 80 70 60 50

40
30 20

Survival functions for time to fluid Clearance as Confirmed by otoscopy

10
0
0

Years
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 gevolgen directe en indirecte kosten antibioticum resistentie

PREVENTIE

Preventie OMA
Benvloeden risicofactoren
Chirurgie Chemoprofylaxie Immunoprofylaxie

1. Benvloeden risicofactoren
Gastheer afwijkingen KNO-gebied immunologische afwijkingen

Omgeving

dagverblijf passief roken fopspeen borstvoeding beschermt

2. Chemoprofylaxie
Meta-analyse (9 studies)

Antibioticum profylaxie OMA / maand

0.11 episodes

Williams et al. JAMA 1993

Antibioticaprofylaxie

Grafiek profylaxis

50 Prophylaxis 4-6 mo

S.pneumo H.flu M.cat

% with resistant strain

40 30 20 10 0| 0
| | | | | | | | |

4 5 Month

Brook CID 1996

Chemoprofylaxie met Xilitol

Cumulative incidence of AOM
0.6 0.5 0.4 0.3 0.2 0.1 0
1 15 30 45 60 75 90

Cumulative incidence of AOM

0.3 -

0.2 control Xylitol 0.1 0

1 15 30 45 60 75 90

Control Xylitol Lozenge

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 chinchillas (Shurin et al. 1988) - kinderen met rec. OMA (Shurin et al.1993) - reduce incidence and severity of RSV lower respiratory tract infections (Simoes et al. 1996)

RSV IG IV

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 Totaal aantal OMA (in influenzae seizoen) :

86% 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
PCV/PSV

Dutch OMAVAX trial

Cumulative hazard

Control

Cumulative hazard

PCV/PSV

Control

n = 78 RR (95% CI): 1,16 (0,69 1,96) Time after complete vaccination Dhooge & Van Kempen, 2002

n = 383 10 RR (95% CI): 1,29 (1,02 1,62) Time after complete vaccination Veenhoven et al, abstract ISPPD, 2002