Changes

August 2024 — reviewed. A literature search was conducted in July 2024 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. The topic has undergone minor restructuring, to improve clarity and navigation. No major changes to recommendations have been made.

Update

Goals

To support primary healthcare professionals to:

• Recognise the clinical features of suspected cholesteatoma.
• Arrange referral to an ear, nose, and throat (ENT) specialist if there is suspected cholesteatoma.
• Arrange emergency hospital admission if there is a suspected serious or life-threatening complication of cholesteatoma.

Outcome measures

Audit criteria

QOF indicators

QIPP - Options for local implementation

NICE quality standards

What is it?

• Cholesteatoma is a benign mass formed by the keratinizing squamous epithelium in the middle ear and/or mastoid air cell spaces, subepithelial connective tissue, and by the progressive accumulation of keratin debris with or without surrounding inflammatory reaction [Olszewska, 2015].
  • It may become infected and locally invasive, eroding through neighbouring structures such as the ossicular chain [Dannatt, 2013; Rutkowska, 2017].
  • It is usually acquired, but can be congenital (rare) [Kuo, 2015; Olszewska, 2015]. Acquired cholesteatoma may affect children and adults and is a subcategory of chronic otitis media. It may be differentiated into [Olszewska, 2015; Rutkowska, 2017]:
    • Attic (extending to the antrum, mastoid, or tympanic cavity).
    • Sinus (extending to the tympanic sinus and posterior portion of the tympanic membrane).
    • Tensa (results from retraction and total adhesion of the pars tensa of the tympanic membrane).

What causes it?

The pathophysiology of cholesteatoma is not completely understood [Olszewska, 2015] [Castle, 2018]. Cholesteatoma is usually acquired, but can be congenital (rare) [Kuo, 2015] [Olszewska, 2015].

• Acquired cholesteatoma is associated with either a retraction pocket of the tympanic membrane, a tympanic membrane perforation, or implantation from trauma or iatrogenic causes [Olszewska, 2015].
  • Primary acquired cholesteatoma develops from a retraction pocket of the pars flaccida and/or pars tensa of the tympanic membrane and is due to dysfunction of the regulation of middle ear pressure and Eustachian tube dysfunction. Over time, the retraction pocket forms a pouch with a narrow neck. The external layer of the tympanic membrane loses its self-cleaning ability and starts the accumulation of keratin debris, leading to the expansion of the lesion and potential erosion of adjacent bony structures [Olszewska, 2015; Castle, 2018]. See the CKS topic on Otitis media with effusion for more information.
  • Secondary acquired cholesteatoma may develop due to the extension of keratinizing squamous epithelium of the tympanic membrane or external ear canal into the middle ear and/or mastoid through a marginal tympanic membrane perforation, as a result of acute or chronic otitis media and ear trauma, or it may be iatrogenic [Olszewska, 2015; Rutkowska, 2017]. See the CKS topics on Otitis media - chronic suppurative and Otitis media with effusion for more information.
• Congenital cholesteatoma is an expanding cystic mass with keratinizing squamous epithelium located medially to the intact tympanic membrane [Olszewska, 2015].
  • It is assumed to be present at birth but is usually diagnosed during infancy or in early childhood in children with no prior history of ear discharge, perforation, or previous ear surgery. It is usually located at the anterosuperior quadrant of the middle ear [Olszewska, 2015].
  • It is thought to arise when squamous epithelium becomes trapped within the middle ear during embryogenesis and then gradually enlarges [Kuo, 2015].

What are the risk factors?

Possible risk factors for cholesteatoma include:

• Male sex — males slightly outnumber females in a ratio of 1.4:1 [Castle, 2018].
• Middle ear disease — cholesteatoma is usually preceded by a history of middle ear disease, such as recurrent otitis media and Eustachian tube dysfunction [Chang, 2008; Castle, 2018; Bouzaher, 2023]. See the CKS topic on Otitis media with effusion for more information.
• Following ear, nose, and throat (ENT) surgery such as tympanoplasty, or following traumatic blast injury to the ear (rare) — may result in implantation of viable keratinocytes into the middle ear cleft [Castle, 2018; Bouzaher, 2023].
• Congenital anomalies and genetic syndromes — anomalies associated with compromised eustachian tube function can increase the risk of cholesteatoma, such as cleft palate, certain craniofacial abnormalities, and Turner or Down syndrome [Chang, 2008; Castle, 2018; Jennings, 2018].

How common is it?

The estimated incidence of cholesteatoma in the literature varies depending on the study type, study population, and geographical location.

• Expert opinion in a review article cites evidence in the literature that [Olszewska, 2004]:
  • The mean annual incidence of cholesteatoma is 3 per 100,000 in children and 9.2 per 100,000 adults in Finland and Denmark.
  • Males slightly outnumber females in a ratio of 1.4:1.
  • It more commonly affects people younger than 50 years of age.
  • The mean age of children affected by congenital cholesteatoma is 5.6 years.
  • The mean age of children affected by acquired cholesteatoma is 9.7 years.
• Expert opinion in a review article notes that cholesteatoma can arise at any age, with peak incidence in the age range of 5–15 years [Bhutta, 2011].
• Expert opinion in a review article states that a general practitioner with a list size of 2500 patients would expect to see on average one new case of cholesteatoma every 4–5 years [Bhutta, 2011].

What is the prognosis?

Following surgical treatment of acquired cholesteatoma, prolonged follow-up is needed to detect possible residual or recurrent disease.

• Residual disease results from incomplete surgical removal of cholesteatoma matrix. Recurrent cholesteatoma originates from the re-formation of retraction pocket after complete surgical removal of the previous cholesteatoma [Olszewska, 2015].
• Expert opinion in a review article notes that the risk of residual disease after corrective surgery depends on the surgical procedure and extent of disease, but may be up to 5–30% [Bhutta, 2011].
• A Danish retrospective, observational follow-up study (n = 147 people following mastoidectomy surgery for cholesteatoma) reported [Britze, 2017]:
  • A 10-year cumulative recurrence rate of 44%.
  • Independent risk factors for recurrence included age younger than 15 years; cholesteatoma localized to the mastoid; and stapes and incus erosion.
  • Of those with recurrent disease, 12% experienced a second recurrence of cholesteatoma within 5 years, and 18% experienced a second recurrence within 10 years of follow-up.
• 7–10% of children with cholesteatoma have simultaneous bilateral cholesteatomas or develop subsequent contralateral cholesteatoma in the other ear during follow-up [Kuo, 2015].
• Pediatric-acquired cholesteatoma is typically more aggressive, more proliferative, and associated with a less favourable prognosis than adult-acquired cholesteatoma [Kuo, 2015].

What are the complications?

Possible complications of cholesteatoma if undetected and untreated include:

• Recurrent ear infections — recurrent infections and inflammatory reaction at the subepithelial connective tissue of cholesteatoma may contribute to the bone resorption in the adjacent area [Olszewska, 2015; Castle, 2018]. See the CKS topics on Otitis media - chronic suppurative and Otitis media with effusion for more information.
• Conductive hearing loss — commonly due to the cholesteatoma mass and/or erosion of the ossicles [Bhutta, 2011; Castle, 2018]. See the CKS topic on Hearing loss in adults for more information.
• Labyrinthine or perilymphatic fistula — if cholesteatoma erodes through the temporal bone or inner ear [Olszewska, 2015; Bouzaher, 2023].
• Acquired cholesteatoma may extend into the middle or posterior cranial fossa if untreated [Olszewska, 2015]. Extensive disease is rare, but may cause:
  • Temporal bone erosion with or without facial palsy — due to damage to the facial nerve as it traverses the middle ear [Bhutta, 2011; Olszewska, 2015; Castle, 2018].
  • Vertigo — due to erosion of the bone which overlies the semicircular canals [Bhutta, 2011; Kuo, 2015]. See the CKS topic on Vertigo for more information.
  • Profound sensorineural hearing loss — due to erosion into the inner ear and damage to the cochlea [Bhutta, 2011; Olszewska, 2015]. See the CKS topic on Hearing loss in adults for more information.
  • Meningitis or intracranial abscess — due to the spread of infection through the roof of the middle ear [Bhutta, 2011; Castle, 2018]. See the CKS topic on Meningitis - bacterial meningitis and meningococcal disease for more information.
  • Mastoiditis — an acute infection of the temporal bone that occurs more commonly in acute otitis media but may occur in chronic otitis media with cholesteatoma [Chang, 2008; Castle, 2018]. See the CKS topics on Otitis media - acute and Otitis media - chronic suppurative for more information.
  • Cavernous sinus thrombosis — a rare infective complication [Castle, 2018].

When should I suspect a diagnosis of cholesteatoma?

Be aware that cholesteatoma may be asymptomatic or present with mild or intermittent symptoms in its early stages, and diagnosis is often delayed.

• Suspect a diagnosis of acquired cholesteatoma if a person presents with possible clinical features due to growth with or without the destruction of adjacent structures:
  • Recurrent or persistent unilateral purulent ear discharge, which does not respond to appropriate treatment for recurrent otitis media or otitis externa. See the CKS topics on Otitis externa and Otitis media - acute for more information.
    • Ear discharge is typically malodorous and scanty.
  • Progressive hearing loss or tinnitus. See the CKS topics on Hearing loss in adults and Tinnitus for more information.
  • Ear pain, vertigo, or facial weakness (due to facial nerve involvement) — may suggest advanced disease. See the CKS topic on Vertigo for more information.
  • Abnormal otoscopic examination, including tympanic membrane perforation. See the section on Assessment for more information.
• Suspect a diagnosis of congenital cholesteatoma if a baby or young child presents with clinical features depending on the location and extent of the lesion:
  • Unilateral conductive hearing loss (rare).
  • Ear pain (very rare).
  • Abnormal otoscopic examination, such as spherical white mass medial to an intact tympanic membrane.

How should I assess a person with suspected cholesteatoma?

If a person has a suspected diagnosis of cholesteatoma:

• Ask about:
  • Any symptoms, duration, severity, and impact on daily functioning.
  • Any pre-existing ear disease such as otitis media with or without effusion, or previous ear, nose, and throat (ENT) surgery.
  • Any risk factors for cholesteatoma.
  • Any features of a complication.
  • Any family history of chronic middle ear disease or cholesteatoma.
• Examine both ears with otoscopy to assess for typical clinical features, such as:
  • A round, white or yellowish mass behind the tympanic membrane.
  • Evidence of a retraction pocket, typically in the attic or posterosuperior quadrant of the tympanic membrane.
    • There may be an accumulation of yellow or white crust/debris visible within the pocket, which may be surrounded by pus (it may resemble the appearance of wax in close association with the tympanic membrane).
    • There may be tympanic membrane perforation adjacent to visible crust.
    • There may be visible erosion of surrounding bone.
  • Note: congenital cholesteatoma (rare) may appear as a spherical white mass behind an intact tympanic membrane, typically in a person with no prior history of ear discharge, tympanic membrane perforation, or ENT surgery.
• Examine the head, neck, and cranial nerves for facial nerve palsy and signs of other complications if there is any suspicion of extensive disease.
• If there is significant discharge in the external ear canal occluding the tympanic membrane:
  • Consider arranging ENT referral for examination with otomicroscopy and micro-suctioning of the ear canal, or
  • Consider empirical treatment for presumed external or middle ear infection, depending on clinical judgement.
    • Treat for otitis externa, particularly if there is inflammation of the ear canal suggested by tenderness and swelling. See the CKS topic on Otitis externa for more information.
    • Treat for acute otitis media if there is acute onset of ear pain associated with purulent ear discharge. See the CKS topic on Otitis media - acute for more information.
• Re-examine the ears after treatment has been completed.
  • If the tympanic membrane cannot be seen clearly still, arrange ENT referral. Do not delay referral by giving repeated courses of treatment if ear discharge persists.

What else might it be?

Alternative conditions which may present similarly to cholesteatoma include:

• Acute otitis media — typically a history of reduced hearing with ear pain that is relieved suddenly and followed by ear discharge and signs of tympanic membrane perforation. On examination, granulation tissue may be visible. See the CKS topic on Otitis media - acute for more information.
• Otitis media with effusion. See the CKS topic on Otitis media with effusion for more information.
• Otitis externa — a diagnosis of cholesteatoma should be considered if presumed otitis externa is not resolving with treatment. See the CKS topic on Otitis externa for more information.
• Necrotising otitis externa — should be excluded if ear pain and discharge do not respond to treatment within 72 hours in a person who is immunocompromised. See the CKS topic on Otitis externa for more information.
• Tympanosclerosis — a white appearance of fibrotic scarring of the tympanic membrane with an irregularly sharp edge, commonly seen after previous episodes of otitis media, trauma to the tympanic membrane, or grommet insertion.
• Osteoma — simple growth of the bone of the ear canal forming a sessile lump.
• Solitary exostoses — often arise from the roof of the bony ear canal.
• Squamous cell carcinoma — malignancy may present with areas of ulceration or granulation tissue in the ear canal and possible blood-stained discharge; there may be distortion of the soft tissue and bone of the ear canal.

Scenario: Suspected cholesteatoma

From birth onwards.

Search strategy

Scope of search

A literature search was conducted for guidelines and systematic reviews on primary care management of cholesteatoma.

Search dates

May 2019 - July 2024

Key search terms

The terms listed below are the core search terms that were used for EBSCOhost MEDLINE (searched 20th May 2019). These were combined with filters to identify guidelines, systematic reviews and primary care relevant literature in EBSCOhost MEDLINE. The strategy was adapted for The Cochrane Library databases. 

S3    S1 OR S2 
S2    AB cholesteatoma* OR TI cholesteatoma* 
S1    (MH "Cholesteatoma+") 

Sources of guidelines

• National Institute for Health and Care Excellence (NICE)
• Scottish Intercollegiate Guidelines Network (SIGN)
• Royal College of Physicians
• Royal College of General Practitioners
• Royal College of Nursing
• NICE Evidence
• World Health Organization
• Guidelines International Network
• TRIP database
• Agency for Healthcare Research and Quality
• Institute for Clinical Systems Improvement
• National Health and Medical Research Council (Australia)
• Royal Australian College of General Practitioners
• British Columbia Medical Association
• Canadian Medical Association
• Alberta Medical Association
• Michigan Quality Improvement Consortium
• Singapore Ministry of Health
• National Resource for Infection Control
• RefHELP NHS Lothian Referral Guidelines
• Medline (with guideline filter)
• Driver and Vehicle Licensing Agency
• NHS Health at Work (occupational health practice)

Sources of systematic reviews and meta-analyses

• The Cochrane Library:
  • Systematic reviews
  • Protocols
  • Database of Abstracts of Reviews of Effects
• Medline (with systematic review filter)
• EMBASE (with systematic review filter)

Sources of health technology assessments and economic appraisals

• NIHR Health Technology Assessment programme
• The Cochrane Library:
  • NHS Economic Evaluations
  • Health Technology Assessments
• Canadian Agency for Drugs and Technologies in Health
• International Network of Agencies for Health Technology Assessment

Sources of randomized controlled trials

• The Cochrane Library:
  • Central Register of Controlled Trials
• Medline (with randomized controlled trial filter)
• EMBASE (with randomized controlled trial filter)

Sources of evidence based reviews and evidence summaries

• Bandolier
• Drug and Therapeutics Bulletin
• TRIP database
• Central Services Agency COMPASS Therapeutic Notes

Sources of national policy

• Department of Health
• Health Management Information Consortium (HMIC)

Patient experiences

• Healthtalk
• BMJ - Patient Journeys

Sources of medicines information

The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.

• British National Formulary (BNF)
• electronic Medicines Compendium (eMC)
• European Medicines Agency (EMEA)
• LactMed
• Medicines and Healthcare products Regulatory Agency (MHRA)
• REPROTOX
• Scottish Medicines Consortium
• Stockley's Drug Interactions
• TERIS
• TOXBASE
• Micromedex
• UK Medicines Information

Stakeholder engagement

Our policy

The external review process is an essential part of CKS topic development. Consultation with a wide range of stakeholders provides quality assurance of the topic in terms of:

• Clinical accuracy.
• Consistency with other providers of clinical knowledge for primary care.
• Accuracy of implementation of national guidance (in particular NICE guidelines).
• Usability.

Principles of the consultation process

• The process is inclusive and any individual may participate.
• To participate, an individual must declare whether they have any competing interests or not. If they do not declare whether or not they have competing interests, their comments will not be considered.
• Comments received after the deadline will be considered, but they may not be acted upon before the clinical topic is issued onto the website.
• Comments are accepted in any format that is convenient to the reviewer, although an electronic format is encouraged.
• External reviewers are not paid for commenting on the draft topics.
• Discussion with an individual or an organization about the CKS response to their comments is only undertaken in exceptional circumstances (at the discretion of the Clinical Editor or Editorial Steering Group).
• All reviewers are thanked and offered a letter acknowledging their contribution for the purposes of appraisal/revalidation.
• All reviewers are invited to be acknowledged on the website. All reviewers are given the opportunity to feedback about the external review process, enabling improvements to be made where appropriate.

Stakeholders

• Key stakeholders identified by the CKS team are invited to comment on draft CKS topics. Individuals and organizations can also register an interest to feedback on a specific topic, or topics in a particular clinical area, through the Getting involved section of the Clarity Informatics website.
• Stakeholders identified from the following groups are invited to review draft topics:
  • Experts in the topic area.
  • Professional organizations and societies (for example, Royal Colleges).
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Clarity Informatics has enlisted the support and involvement of patients and lay persons at all stages in the process of creating the content which include:

• Topic selection
• Scoping of topic
• Selection of clinical scenarios
• First draft internal review
• Second draft internal review
• External review
• Final draft and pre-publication

Our lay and patient involvement includes membership on the editorial steering group, contacting expert patient groups, organizations and individuals.

Evidence exclusion criteria

Our policy

Scoping a literature search, and reviewing the evidence for CKS is a methodical and systematic process that is carried out by the lead clinical author for each topic. Relevant evidence is gathered in order that the clinical author can make fully informed decisions and recommendations. It is important to note that some evidence may be excluded for a variety of reasons. These reasons may be applied across all CKS topics or may be specific to a given topic.

Studies identified during literature searches are reviewed to identify the most appropriate information to author a CKS topic, ensuring any recommendations are based on the best evidence. We use the principles of the GRADE and PICOT approaches to assess the quality of published research. We use the principles of AGREE II to assess the quality of published guidelines.

Standard exclusions for scoping literature:

• Animal studies
• Original research is not written in English

Possible exclusions for reviewed literature:

• Sample size too small or study underpowered
• Bias evident or promotional literature
• Population not relevant
• Intervention/treatment not relevant
• Outcomes not relevant
• Outcomes have no clear evidence of clinical effectiveness
• Setting not relevant
• Not relevant to UK
• Incorrect study type
• Review article
• Duplicate reference

Organizational, behavioural and financial barriers

Our policy

The CKS literature searches take into consideration the following concepts, which are discussed at the initial scoping of the topic.

• Feasibility
  • Studies are selected depending on whether the intervention under investigation is available in the NHS and can be practically and safely undertaken in primary care.
• Organizational and Financial Impact Analysis
• Studies are selected and evaluated on whether the intervention under investigations may have an impact on local clinical service provision or national impact on cost for the NHS. The principles of clinical budget impact analysis are adhered to, evaluated and recorded by the author. The following factors are considered when making this assessment and analysis.
  • Eligible population
  • Current interventions
  • Likely uptake of new intervention or recommendation
  • Cost of the current or new intervention mix
  • Impact on other costs
  • Condition-related costs
  • In-direct costs and service impacts
  • Time dependencies
• Cost-effectiveness or cost-benefit analysis studies are identified where available. 

We also evaluate and include evidence from NICE accredited sources which provide economic evaluations of recommendations, such as NICE guidelines. When a recommended action may not be possible because of resource constraints, this is explicitly indicated to healthcare professionals by the wording of the CKS recommendation.

Declarations of interest

Our policy

Clarity Informatics requests that all those involved in the writing and reviewing of topics, and those involved in the external review process to declare any competing interests. Signed copies are securely held by Clarity Informatics and are available on request with the permission of the individual. A copy of the declaration of interest form which participants are asked to complete annually is also available on request. A brief outline of the declarations of interest policy is described here and full details of the policy is available on the Clarity Informatics website. Declarations of interests of the authors are not routinely published, however competing interests of all those involved in the topic update or development are listed below. Competing interests include:

• Personal financial interests
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Although particular attention is given to interests that could result in financial gains or losses for the individual, competing interests may also arise from academic competition or for political, personal, religious, and reputational reasons. An individual is not obliged to seek out knowledge of work done for, or on behalf of, the healthcare industry within the departments for which they are responsible if they would not normally expect to be informed.

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Any individual (or organization) involved in developing, reviewing, or commenting on clinical content, particularly the recommendations should declare competing interests. This includes the authoring team members, expert advisers, external reviewers of draft topics, individuals providing feedback on published topics, and Editorial Steering Group members. Declarations of interest are completed annually for authoring team and editorial steering group members, and are completed at the start of the topic update and development process for external stakeholders.

Competing interests declared for this topic:

None.