Practice Essentials
Inflammatory diseases of the middle ear include a broad range of pathologic conditions, including acute otitis media (AOM; suppurative or nonsuppurative), bullous myringitis, granular myringitis, eosinophilic otitis media, and chronic suppurative otitis media (CSOM), with or without cholesteatoma. The range and complexity of the problems that can arise pose a challenge to the clinician, who sometimes has only subtle clues that lead to the discovery of extensive disease. [1, 2, 3, 4, 5, 6]
AOM is characterized by a short-lived infection (< 3 mo) that may be initially viral and then bacterial in origin. [7] Patients generally experience pain and some hearing loss and often develop a fever. Discharge from the ear usually accompanies this infection in patients with acute suppurative otitis media. [8]
CSOM has traditionally been classified into safe ear disease and unsafe ear disease. Safe ear disease, sometimes called tubotympanic disease, is characterized as a central perforation of the pars tensa, with the inflammatory process affecting the mucosa of the middle ear cleft. Unsafe ear disease, sometimes called atticoantral disease, is typified by a marginal perforation of the posterosuperior pars tensa or pars flaccida. Cholesteatoma is frequently present in CSOM with posterosuperior perforations. Partially due to induced bony erosion and secondary infection, cholesteatomas can lead to potentially devastating sequelae. Admittedly, all cases of CSOM, including those described above as safe, can be associated with serious intracranial complications. Therefore, the term safe does not adequately categorize any cases of CSOM.
CSOM can be more simply divided into mucosal disease and cholesteatoma. Mucosal disease is typified by a bacterial infection of the middle ear cleft with the presence of pus, associated with discharge through a pars tensa perforation, for longer than 3 months. Acquired cholesteatoma, usually arising from the pars flaccida skin, typically involves the epitympanum and the mastoid antrum and, as stated above, can be erosive, causing serious complications.
Eosinophilic otitis media is an intractable middle ear disease associated with bronchial asthma and nasal allergy that sometimes induces deterioration of sensorineural hearing loss. [9] How eosinophils accumulate in the middle ear has yet to be determined; active eosinophilic inflammation may occur in the entire respiratory tract, including the middle ear, in patients with this disease. EOM often produces a yellow and highly viscous middle ear effusion and can cause symptoms that range from prolonged hearing loss and otorrhea to sudden deafness. The middle ear symptoms are unresponsive to conventional treatments for otitis media and are instead treated with steroids. [10, 11]
The following image depicts the middle ear.
Middle ear anatomy.
Signs and symptoms of inflammatory disease of the middle ear
The earliest clinical manifestation of acute suppurative otitis media is a sense of fullness in the ear with some conductive hearing loss. An earache may be present but is not severe.
The two classic symptoms of CSOM (mucosal disease) are otorrhea and hearing loss, which can affect one or both ears.
The main symptom of CSOM with cholesteatoma is purulent otorrhea, with or without associated conductive hearing loss.
Workup in inflammatory disease of the middle ear
Culturing of the discharge after a spontaneous perforation in patients with acute suppurative otitis media is reliable only in the first few hours because external ear canal flora contaminates the otorrhea.
Computed tomography (CT) scanning is generally the imaging modality of choice in the assessment of cholesteatoma.
High-resolution CT scanning has allowed better detection of acute otomastoiditis, while gadolinium-enhanced magnetic resonance imaging (MRI) is currently the imaging modality of choice to aid in the diagnosis of intracranial venous thrombosis and intracranial abscess.
With regard to histologic findings, the degree of inflammation in CSOM without cholesteatoma is related to clinical activity, with the most intense changes seen in ears with continuous otorrhea.
Cholesteatomatous CSOM appears macroscopically as a crystallike structure with pale debris in the middle ear cleft.
Management of inflammatory disease of the middle ear
Medical care
The role of antibiotics in the treatment of AOM remains ill defined because studies have shown that antibiotics do not affect the outcome.
Some physician groups advocate observation and withholding antibiotics in children with uncomplicated AOM and no comorbid factors. [12] The withholding of antibiotics is based on diagnostic certainty, age, severity of the illness, and means for adequate follow-up. Observation involves monitoring the child for resolution of symptoms within 48-72 hours and reevaluating the patient at this time.
Guidelines from the American Academy of Pediatrics and American Academy of Otolaryngology-Head and Neck Surgery have helped to clarify whom to definitely treat with antibiotics. For infants younger than 6 months, prescribing antibiotics is still recommended because of the increased risk of complications in this age group, even if the diagnosis of AOM is uncertain. If the child is aged 6 months to 2 years and is severely ill (fever ≥ 39°C or moderate to severe otalgia) and the diagnosis of AOM is uncertain, antibiotics should be considered.
Topical liquid agents used in the treatment of chronic middle ear disease include a combination of antibiotics, antifungals, antiseptics, solvents, and steroids. The most commonly used topical antibiotics for CSOM include quinolone derivatives, such as ciprofloxacin and ofloxacin (eg, Cipro HC Otic, Floxin), and aminoglycosides.
Surgical care
Myringotomy is a technique in which an incision is made in the tympanic membrane to adequately drain the middle ear.
Myringotomy is reserved for AOM associated with severe otalgia or high fever in patients who have had a poor response to antibiotics. Myringotomy is also indicated when a suppurative complication is present, in children who are acutely ill, in cases of AOM that occur during antibiotic treatment, in newborns, and in patients with primary or secondary immunodeficiency in whom an unusual organism may be present.
Transtympanic ventilation tubes may be used to prevent recurrent AOM, even in the absence of a middle ear effusion, although the reason for this remains unclear.
Pathophysiology
The ciliated, pseudostratified columnar epithelium of the respiratory tract extends up the eustachian tube as far as the anterior part of the middle ear cavity. Because of the presence of goblet cells and mucus-secreting glands, this epithelium is capable of mucus production. More posteriorly, the mucosa changes patchily into a simple cuboidal or stratified epithelium with no secretory elements. The medial aspect of the tympanic membrane and the mastoid air cells are lined by a single layer of cells that range in shape from cuboidal to flat.
In the early stages of inflammation, regardless of cause, vasodilatation of the submucosal tissues occurs. Glandular secretion is stimulated with the production of a thin mucoid fluid. Some epithelial cells die, and bacteria that are usually in the area multiply in the denuded areas and aggravate the condition. The neutrophils in the blood cause a polymorphonuclear reaction, resulting in a mucopurulent discharge. This discharge may remain stagnant within the middle ear and the mastoid air cell system because of immobility or loss of the cilia, including those in the eustachian tube.
Resolution frequently occurs, but, if the condition is prolonged for some reason, such as the inability of the secretions to drain down the eustachian tube, the number of glands and goblet cells increases, and the areas formerly covered by a cuboidal or flat epithelium change into areas of a similar but perhaps less well-differentiated pseudostratified columnar epithelium. Differentiation into squamous epithelium, most frequently nonkeratinized, can also occur.
Granulation tissue results from the nonresolution of an inflammatory process. Localized areas of the mucosa become hyperplastic with invasion of fibroblasts, capillaries, macrophages, plasma cells, and lymphocytes. Granulation tissue can be covered by all the mucosal types described above, but, because the tissue is frequently ulcerated, it does not have a mucosal covering.
Anatomical considerations also contribute to the pathophysiology of middle ear diseases. The eustachian tube is important in pressure regulation of the middle ear, protection from nasopharyngeal sound pressure and secretions, and clearance (into the nasopharynx) of secretions produced within the middle ear. The eustachian tube has been found to be highly compliant in infants and young children, providing the eustachian tube with an abnormal patency. Greater patency of the eustachian tube allows not only gas to readily flow from the nasopharynx into the middle ear but also easier access for unwanted secretions from the nasopharynx. This increases the likelihood of infection.
The length of the eustachian tube is another key anatomical consideration in the pathogenesis of middle ear inflammatory disorders. The shorter the tube, the more likely secretions can reflux into the middle ear. For instance, young children with a cleft palate and those with Down syndrome have eustachian tubes that are statistically shorter than those of age-matched controls younger than 6 years, which may explain the frequent occurrence of troublesome otorrhea in these populations.
Various chemical mediators of inflammation have been described and categorized into the following groups:
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Histamine
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Lipid mediators
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Plasma enzyme systems
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Kinins
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Cytotoxins
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Neurogenic substances
Various interleukins are of particular importance in otitis media. An example of the recent ongoing work in this field is the discovery that the bone-resorbing activity of cholesteatoma with chronic otitis media may be attributed to interleukin-1 α (IL-1 α).
Epidemiology
Frequency
United States
One third of all antibiotics purchased for children are for the treatment of otitis media. [13]
The Center for Disease Control (CDC) showed that otitis media was the principal diagnosis for 12% of ambulatory-care visits provided to children younger than 15 years.
AOM accounts for 24 million pediatric office visits and $5 billion in costs annually. A study by Tong et al indicated that in the United States between 2008 and 2014, healthcare use associated with AOM reached a mean annual incidence of 60.5 AOM cases per 1000 person-years, with this rate varying little over the investigation period. The greatest share of this utilization involved office/outpatients visits (55.7 cases per 1000 person-years). The study estimated that AOM affects 19.5 million patients each year in the United States. [14]
A study of cholesteatoma in the United States revealed an incidence of 6 cases per 100,000 population. Within this population, cholesteatoma was most common in children aged 10-19 years, with an incidence of 9.2 cases per 100,000 population.
International
A study by Hullegie et al found that during the coronavirus disease 2019 (COVID-19) pandemic, the incidence of otitis media among children aged 0-12 years declined in the Netherlands. In this pediatric population, before the pandemic, the incidence rate for AOM per 1000 child-years was 73.7, versus 27.1 during the pandemic, while the incidence rates per 1000 child-years for otitis media with effusion (OME) were 9.6 versus 4.1, respectively. [15]
Mortality/Morbidity
Since the advent of the antimicrobial era, the mortality rate associated with complications of middle ear inflammatory disorders has dramatically decreased. The mortality rates associated with otitis media and mastoiditis decreased from about 2 per 100,000 persons in 1936 to less than 0.01 per 100,000 persons in 1976.
Between 2000 and 2012, a period marked by the rise in the use of pneumococcal conjugate vaccines, pediatric mastoiditis in the United States reached its highest incidence in 2006 (2.7 per 100,000 population), while the lowest incidence was seen in 2012 (1.8 per 100,000 population). [16]
The 2 most common complications of suppurative otitis include mastoiditis and facial paralysis. [17] In developing nations, these complications remain relatively common because of the lack of adequate primary care. According to studies in developing countries, the rate in some communities was as high as 33% for perforation of the tympanic membrane, 6% for otorrhea, and 5% for mastoiditis.
Cholesteatoma, atticoantral mucosal disease, and acute suppurative otitis media cause complications by spread of infection.
Complications of CSOM are associated with high morbidity and may be life threatening. In a retrospective study, Browning calculated that the risk of a patient with CSOM developing an intracerebral abscess is 1 in 3500. [18]
Extracranial complications include chronic otitis externa and meatal stenosis, ossicular discontinuity due to ossicular erosion, middle ear adhesions, tympanosclerosis, otosclerosis, mastoid tip (Bezold) abscess, lower motor neuron facial nerve palsy, serous or purulent labyrinthitis, petrositis, Gradenigo syndrome, and labyrinthine fistula. All of these represent significant morbidity to the patient.
Intracranial complications include lateral (transverse and sigmoid) sinus thrombosis; meningitis; extradural, subdural, or intracerebral (cerebellar and temporal lobe) abscess; and otitic hydrocephalus. In a study of patients with chronic middle ear disease and cholesteatoma, 7.5% developed intracranial complications. A 2009 study by Dubey et al revealed that the most common complication was meningitis. [19]
Race
American Indians and Canadian Inuits have a strikingly high incidence of acute suppurative otitis media. In children of African and Australian Aboriginal origin, middle ear infections are more commonly severe. African American children seem to have fewer episodes of middle ear infections than American white children.
CSOM suppurative otitis media without cholesteatoma is extremely common in certain racial groups, including American Indians, Canadian Inuits, Alaskan Inuits, Australian Aborigines, and New Zealand Maoris.
In racial groups with a high incidence of central tympanic membrane perforations, such as North American Inuits and Australian Aborigines, cholesteatoma is relatively uncommon.
Sex
In most studies on the incidence of acute suppurative otitis media, little difference exists between males and females.
Age
See the list below:
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AOM falls into 2 distinct age groups; it is more common in the younger group (0-5 y) than in the older group (5-11 y). By age 6 months, about 25% of all children have had 1 or more episodes of AOM. At age 1 year, this figure rises to 62%; by age 3 years, to 81%; and by age 5 years, to 91%. After age 7 years, the incidence declines.
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The combined results of selected published studies on CSOM showed a bimodal prevalence curve with peaks of 20% at age 2 years and 15% at age 5 years.
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Middle ear anatomy.
