xRead - January 2023

Assessment and management of chronic otitis externa Bradley W. Kesser

Purpose of review Chronic otitis externa (COE) remains a frustrating problem for both patient and physician. The end stage of disease, medial fibrosing otitis externa, is very challenging to repair. New and old therapies and promising approaches to the treatment of this often recalcitrant problem are presented in this review. Recent findings Tacrolimus, a nonsteroidal immunosuppressant, and fluocinolone acetonide oil 0.01%, a medium-high potency steroid preparation, may offer additional therapeutic options in the struggle against this inflammatory ear canal/skin condition of often unknown cause. Relative potencies of many steroid preparations will be presented along with several treatment strategies for controlling COE. Underlying autoimmune problems such as Sjo¨ gren’s disease, sarcoidosis, and amyloidosis must be searched and, if present, addressed and treated for resolution of symptoms. Cutting edge therapies, including use of bacteriophages and inflammatory proteases, will also be reviewed. Summary No single therapy will be successful for every patient with COE. The search for an underlying cause, the removal of all possible irritants to the ear canal skin (e.g. Q-tips, water), debridement, and both topical and occasionally, systemic therapy will control (not cure . . . ) the disease process in the vast majority of patients. Keywords atopy, chronic otitis externa, contact dermatitis, dermatophytid, ear canal, eczema, medial fibrosing otitis externa, otomycosis, seborrhea, topical steroids

Department of Otolaryngology-Head and Neck Surgery, University of Virginia Health System, Virginia, USA Correspondence to Bradley W. Kesser, MD, Department of Otolaryngology-Head and Neck Surgery, University of Virginia Health System, Box 800713, Charlottesville, VA 22908, USA Tel: +1 434 924 2040; fax: +1 434 982 3965; e-mail: Bwk2n@virginia.edu

Current Opinion in Otolaryngology & Head and Neck Surgery 2011, 19:341–347

Curr Opin Otolaryngol Head Neck Surg 19:341–347 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins 1068-9508

COE. Patients may also develop intervening acute infec tions that typically respond to standard therapy for acute otitis externa (thorough debridement, ototopical anti biotic drops, dry ear precautions, and cessation of instru mentation of the canal). Physical exam is characterized by two predominant forms: the ear with seborrhea is charac terized by a lack of cerumen, some clear drainage, but mostly flaky, dry, scaly, erythematous ear canal skin (Fig. 1), or skin with a ‘pasty’, almost shiny appearance. Alternatively, the ear with eczematous inflammation is characterized by weepy, moist, erythematous, tender skin of the ear canal which may also spread to involve the auricle (perichondritis; Fig. 2). The ear canal of patients with chronic fibrosing otitis externa (see below) shows a thickened, erythematous tympanic membrane and medial canal skin often with mucopus or dried mucus casts. The canal seems to taper medially, and conductive hearing loss ensues as the vibratory capacity of the tympanic membrane is com promised by the vigorous deposition of fibrous tissue; this process rarely involves the middle ear.

Introduction Chronic otitis externa (COE) may best be characterized by what it is not – it is not an acute, painful infectious process of the ear canal (acute otitis externa), and it is not an invasive, erosive, inflammatory/infectious condition involving the bony skull base (malignant otitis externa/ skull base osteomyelitis). Rather, COE is an inflamma tory condition of the ear canal skin of unknown, possibly allergic or autoimmune, etiology affecting 3–5% of the population. Clinical characteristics The course of COE can smolder or wax and wane for years with intercurrent exacerbations requiring aggres sive medical management; COE has been associated with poor quality of life [1]. The condition is bilateral in at least half of patients. Patients present with pruritis of the affected ear(s), clear or seromucinous drainage, and aural fullness. If acutely edematous, a conductive hearing loss and pain may also be present, but pain is not typical of

1068-9508 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins

DOI:10.1097/MOO.0b013e328349a125

Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

342 Otology and neuro-otology

Figure 1 ‘Dry’ chronic otitis externa characterized by scaly, flaky, pruritic, erythematous ear canal skin that can extend to the concha, sometimes ascribed to seborrheic dermatitis

Chronic otitis externa may be associated with middle ear disease that causes chronic drainage through a tympanic membrane perforation (chronic suppurative otitis media) or a wet, draining mastoid cavity. It has also been associ ated with cerebrospinal fluid otorrhea [2] and a salivary fistula through a patent foramen of Huschke [3 ]. Systemic disorders such as amyloidosis [4 ], sarcoidosis [5], Sjo¨gren’s disease [6], Wegener’s granulomatosis [7], or atopy [8–10] can underlie COE, or it may be an isolated condition. In general, treatment is aimed at quelling the inflammatory activity in the skin, removing any inciting factors, and searching for causative factors that predispose or exacer bate this often frustrating condition. Chronic otitis externa can wax and wane for years, and a subset of patients will develop chronic fibrosing otitis externa, a condition in which the epithelium of the medial ear canal and tympanic membrane undergo con tinuous, progressive deposition of fibrous tissue/scar, with the end result a blind ending canal with a moderate conductive hearing loss. Cause The cause of COE is unknown and may be multifactorial. Inflammation, rather than true infection, is characteristic, but the cause of the inflammatory response is idiopathic. The association of COE with allergic disease, contact dermatitis, and other systemic autoimmune disorders The goal of treatment is control of the inflammation by removing any offending agents (including Q-tips and water), controlling systemic autoimmune pro blems, careful debridement, and topical therapy. A multitude of topical therapies have been advo cated, including chloromycetin-sulfanilamide-fun gizone-hydrocortisone (CSF-HC) powder, topical steroid creams of varying potency, antibiotic-steroid ototopical preparations, immunosuppressive agent (e.g. tacrolimus) and alcohol-acetic acid drops; find ing one that works for each patient is key. Bacteriophage therapy and protease therapy hold promise in the future for controlling this often frustrating condition. Key points The diagnosis of chronic otitis externa (COE) must be differentiated from acute otitis externa and malignant (necrotizing) otitis externa/skull base osteomyelitis; pain is not a typical feature of COE, but pruritis often is. Treatment of COE is aimed at identifying an underlying cause for the inflammatory skin reaction, whether systemic autoimmune disease such as Wegener’s granulomatosis, contact allergen such as neomycin, fungal infection, or fungal reaction such as the dermatophytid reaction.

Courtesy of Kenneth Greer, MD, Division of Dermatology, Department of Medicine, University of Virginia.

Figure 2 ‘Wet’ chronic otitis externa characterized by weepy, moist, erythematous ear canal skin extending out to the concha, sometimes referred to as an ‘eczematoid ear’

Courtesy of Kenneth Greer, MD, Division of Dermatology, Department of Medicine, University of Virginia.

Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

Assessment and management of chronic otitis externa Kesser 343

such as Wegener’s granulomatosis certainly suggests an autoimmune process. The causative epitopes remain elusive, although fungal antigens, including those else where in the body such as a low-grade onychomycosis, have been suggested [11]. In some patients, those with nickel or neomycin allergy, the obvious causative agent is obviously the contact aller gen [9]. Epicutaneous patch test positivity was statistically higher in patients with chronic eczematous external otitis than in healthy controls, and those patch test positive external otitis patients had a higher recurrence rate (attack rate) than those who were patch test negative [10]. In most patients, however, the agent (if one at all) remains a mystery. Some patients with COE exhibit food hypersen sitivity; both epicutaneous prick test positivity and IgE seropositivity were statistically higher in patients with COE compared with controls in one study [12]. Food hypersensitivity may also play a role in those patients exhibiting the dermatophytid reaction (see below; [11]). Nevertheless, even if the agent is not readily apparent, a careful historical search may reveal the inciting factor. Whereas exogenous causes certainly play a role in COE, some investigators have examined endogenous factors – are the ears of patients with COE fundamentally different? Cerumen has been found to be bactericidal against strains of Pseudomonas , Staphylococcus , and Candida but with low activity against Escherichia coli [13 ]. Yet, when the bac tericidal activity of cerumen against Staphylococcus aureus , S. epidermidis , E. coli , Pseudomonas aeruginosa , and Enter ococcus of otitis externa patients was comparedwith that of healthy volunteers, only the activity against E. coli was statistically different; the authors concluded that theywere not able to confirm that cerumen from patients with recurrent otitis externa had less bactericidal activity than that from a healthy population [14]. What the authors did not address was a quantitative analysis – do patients with COE make less cerumen than healthy patients, and, if so, why? Relative humidity was found to be higher in abnor mal ears (mastoid cavities, ears with tympanic membrane perforation, as well as ears with COE) compared with normal ears [15], and pH was found to be higher in ears with COE compared with control ears [16]. Lowering the pH of the external canal to create an inhospitable environ ment for pathogenic organisms is the foundation for treat ment with topical acetic acid (e.g. acetasol, vosol). Q-tip use can most certainly incite inflammation in the canal skin.Whether an incitingagent or exacerbatingagent, Q-tip use cessation must be a strong recommendation.

Clinically, otomycosis behaves more like COE than acute otitis externa. Hallmark symptoms include intense prur itis, aural fullness, and drainage, often clear. Debris can be so abundant as to cause a conductive hearing loss. Hyphae are often seen on the superficial layer of the debris. Aspergillus and Candida species are the most fre quently isolated fungi. Otomycosis can appear after a course of ototopical antibiotic eardrops, as the bacteri cidal activity of the drops allows fungal overgrowth; it can appear in a patient with a longstanding tympanic mem brane perforation that begins to drain; or it can occur de novo . Otomycosis in the presence of a mastoid cavity is harder to eradicate [17]. Otomycosis can also be a com ponent of a more systemic fungal inflammatory process, fungal allergy, or autoimmune disorder, or a dermatophy tid reaction. Treatment of fungal otitis externa relies on meticulous cleaning of the canal under binocular microscopy. The key to the cleaning is the elevation of the dead skin layer under all the fungal debris. The skin is carefully elevated with a small right angle hook laterally and a plane of dissection is established between the dead skin layer and the healthy (although generally erythematous) skin underneath. The elevation proceeds down the medial canal, and many times a dead skin layer can be elevated off the tympanic membrane. Once all the fungal debris has been removed, the canal can be powdered with a mixture consisting of chloromy cetin 50mg, sulfanilamide 50mg, fungizone 50mg, and hydrocortisone 1mg (‘CSF-HC’). Alternatively, cresylate can be used, but not in the ear with a tympanic membrane perforation. Gentian violet is also an excellent antifungal and drying agent (the vehicle is alcohol) and can be painted throughout the canal skin with a small ‘home made Q-tip’, a straight pick wrapped by cotton. With careful and complete cleaning and a single application of one of these medications coupled with compulsive dry ear precautions and Q-tip cessation, otomycosis can generally be brought to resolution without further treat ment. Antifungal preparations such as clotrimazole, fluconazole, miconazole, or tolnaftate can be used for more recalcitrant patients. These formulations come in creams, gels, oint ments, and solutions. Drug vehicle is an important con sideration, especially in patients with a tympanic mem brane perforation; creams are preferred. Ototoxicity is another consideration; clotrimazole, miconazole, bifona zole, and tolnaftate have a broad spectrum of activity against molds, yeasts, fungi, and dermatophytes, high cure rates, low ototoxicity, greater compliance, and commercial availability as a solution [18 ]. One study found topical ketoconazole to have a higher resolution rate and lower recurrence rate than cresylate drops or aluminum acetate

Otomycosis Fluffy, cotton-like debris in the external auditory canal (EAC) is classic for otomycosis, fungal otitis externa.

Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

344 Otology and neuro-otology

drops [17], whereas another found voriconazole to have more potent in-vitro activity than itraconazole against all Aspergillus species and Candida albicans (all species were resistant to fluconazole in this study) [19 ]. Some patients may require close follow-up for repeated meticulous cleanings under binocular microscopy. An excellent, very effective ‘home remedy’ for persistent otomycosis is a 1 : 1 mixture of isopropyl (rubbing) alcohol and acetic acid (white vinegar; not to be used in a patient with a tympanic membrane perforation). A dropper is useful to place 3–4 drops twice a day for a week. The alcohol removes water and moisture in the canal; the acetic acid lowers the pH of the canal, making it inhos pitable for fungal organisms. Patients are warned that the mixture is very effective but they may smell like a crouton in a salad! As with any acute or chronic ear canal process, dry ear precautions and Q-tip cessation are mandatory. Dermatophytid reaction In patients whose COE is refractory to conventional therapy of debridement, ototopical drops, and/or steroid creams, a low-grade fungal infection elsewhere in the body (e.g. onychomycosis) can set up an inflammatory, allergic reaction in the ear canals. The true incidence of this process is unknown, but it can be easily screened (by exploring other possible areas of fungal infection in the patient such as the nails, scalp, or skin) and often successfully treated. Conditions necessary for a dermatophytid reaction include a primary fungal infection remote from the dermatophytid reaction (e.g. finger/toenails), absence of fungi at the dermatophytid reaction site (ears), resolution of the inflam mation when the primary fungal infection has been era dicated, and a type I Gel and Coombs (IgE) intradermal skin response to the fungal antigen. Elevated serum IgE level is also a good indicator of the role of atopy in the patient’s disease. Most common fungi – TOE (Tricho phyton, Candida, and Epidermophyton) – can be easily treated with either topical or systemic antifungals. If a dermatophytid reaction is diagnosed as the cause of COE, treatment is initially aimed at the primary fungal infection. Since the reaction in the ears is an allergic reaction, allergy management is critical. Frontline therapy for any allergic patient is environmental control. Yeast elimination diet has been strongly advocated [11]. Medical therapy involves meticulous debridement and topical steroids. Betamethasone 0.1% cream, triamcino lone cream, clobetasol, and fluocinolone acetonide oil 0.01% have been advocated. Finally, for refractory patients, especially with high serum IgE, immunotherapy has been shown to be successful [11,20].

Chronic (medial) fibrosing otitis externa A subset of patients, including children [21], with COE will show unrelenting progression of inflammation in the medial canal. After years of cleaning, topical therapy, even systemic therapy, the inflammatory pro cess becomes fibrotic, causing a thickening and scarring of the tympanic membrane and medial canal skin. Computed tomography (CT) imaging shows complete, circumferential opacification of the medial ear canal – a fibrous plug – with a perfectly aerated middle ear space without bony erosion (Fig. 3). This stage – the end result – is characterized by the resolution of the inflammation and drainage with a clean, dry, blind ending ear canal with a mild-to-moderate conductive hearing loss. Surgery is typically not advisable in the acute inflamma tory stage; a technically skillful operation with an initially promising result may succumb to the same inflammatory process. In addition, repair of medial fibrosing otitis externa secondary to a systemic autoimmune disorder (e.g. sarcoidosis) may also fail over time. After years of drainage, drops, and debridement, most patients are so happy to have a dry ear, the conductive hearing loss is not as big an issue. With a dry canal, a conventional hearing aid or a bone anchored hearing aid may offer quite adequate hearing rehabilitation. Should surgery be undertaken, most authors agree that the entire fibrous plug and all involved skin must be removed with formal canalplasty, followed by resurfacing with epithelium, most commonly, a split thickness skin graft [22–24]. One group of authors recommended aggressive treatment of methicillin-resistant Staph. aureus (MRSA) infection with vancomycin both preoperatively and at least

Figure 3 Coronal computed tomography showing the ‘fibrous plug’ at the medial end of the ear canal – opacification up to the medial aspect of the tympanic membrane sparing the aerated middle ear space

Courtesy of Prashant Raghavan, MD, Division of Neuroradiology, Department of Radiology, University of Virginia.

Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

Assessment and management of chronic otitis externa Kesser 345

Table 1 Topical steroids and their potency Brand name

10 days postoperatively [25]. Good surgical outcomes, including hearing improvement, can be achieved with a low complication rate, and a recurrence rate of approxi mately 10–20% [22,24].

Generic name

Class 1 – superpotent Cormax cream/solution, 0.05%

Clobetasol propionate

Diprolene ointment, 0.05%

Betamethasone dipropionate

Temovate cream/ointment/ solution, 0.05%

Clobetasol propionate

Treatment of chronic otitis externa The cornerstone of therapy for COE is the removal of any and all real or potential irritants, including Q-tips, water, medications, soaps, shampoos, bobby pins, fin gernails, paper clips, eyeglass arms, and so on. The vast number of medical therapies for COE only verifies its frustrating, recalcitrant nature. Trial and error may be the most helpful treatment advice. There is a large armamentarium for this disease – find a therapy that works for each patient. Topical steroid therapy has shown efficacy and can be applied in the office under binocular microscopy with a homemade Q-tip. Medium and high potency steroid preparations (creams pre ferred) that have shown efficacy include betamethasone valerate 0.1% and triamcinolone 0.1%. Unpublished data (Magit et al. ) have shown promising results with fluocinolone acetonide oil 0.01% ear drops (Derm-Otic, Hill Dermaceuticals, Sanford, FL). Patients are instructed to wash their hands and apply a small amount of the steroid cream on the end of their pinky finger and apply to the skin at the meatus twice a day. Higher potency drops and creams such as clobetasol propionate 0.05% (supplied as cream, ointment, or gel) and dexa methasone 0.1% ophthalmic drops can be used for breakthrough therapy for short periods of time weighed against the potential side effects of thinning and weak ening of the ear canal skin (Table 1). A course of oral steroids may also help cool down the refractory patient [26]. Tacrolimus (FK-506) 0.1% is a nonsteroidal immunosup pressant mainly used after allogeneic organ transplan tation. It has been shown to have efficacy in atopic dermatitis and recently in noninfectious chronic otitis externa [27] by inserting a wick containing 0.1% tacro limus into the ear canal and changing the wick every second to third day for 9–12 days. Patients with more refractory problems are queried for history of allergic disease, new soaps, detergents, sham poos, food sensitivity, and so on in an effort to identify an inciting agent. Consultation with an allergist may reveal chemical or food sensitivities that can be addressed with environmental control measures and even immunother apy/desensitization. Patients are also queried about remote fungal infections, and the finger and toenails are inspected for low-grade fungal infection. If found, treatment of the low-grade fungal infection, skin end point titration testing, immunotherapy, and the yeast free diet are recommended.

Ultravate cream/ointment, 0.05%

Halobetasol propionate

Vanos cream, 0.1%

Fluocinonide

Psorcon ointment, 0.05% Psorcon E ointment, 0.05% Class 2 – potent Diprolene cream AF, 0.05%

Diflorasone diacetate Diflorasone diacetate

Betamethasone dipropionate

Elocon ointment, 0.1% Florone ointment, 0.05% Halog ointment/cream, 0.1% Lidex cream/gel/ointment, 0.05%

Mometasone furoate Diflorasone diacetate

Halcinonide Fluocinonide

Psorcon cream, 0.05%

Diflorasone diacetate

Topicort cream/ointment, 0.25%

Desoximetasone Desoximetasone

Topicort gel, 0.05%

Class 3 – upper mid-strength Cutivate ointment, 0.005% Lidex-E cream, 0.05% Topicort LP cream, 0.05% Class 4 – mid-strength Cordran ointment, 0.05% Kenalog cream/spray, 0.1% Synalar ointment, 0.03% Westcort ointment, 0.2% Elocon cream, 0.1%

Fluticasone propionate

Fluocinonide

Desoximetasone

Flurandrenolide

Mometasone furoate Triamcinolone acetonide Fluocinolone acetonide Hydrocortisone valerate

Class 5 – lower mid-strength Cordran cream/lotion/tape, 0.05% Flurandrenolide Cutivate cream/lotion, 0.05%

Fluticasone propionate

DermAtop cream, 0.1% DesOwen lotion, 0.05%

Prednicarbate

Desonide

Locoid cream/lotion/ointment/ solution, 0.1%

Hydrocortisone

Pandel cream, 0.1%

Hydrocortisone

Synalar cream, 0.03%/0.01%

Fluocinolone acetonide Hydrocortisone valerate

Westcort cream, 0.2%

Class 6 – mild Aclovate cream/ointment, 0.05% Derma-Smoothe/FS oil, 0.01% Synalar cream/solution, 0.01% Class 7 – least potent Cetacort lotion, 0.5%/1% Cortaid cream/spray/ointment Hytone cream/lotion, 1%/2.5% Micort-HC cream, 2%/2.5% Nutracort lotion, 1%/2.5% Synacort cream, 1%/2.5% Desonate gel, 0.05%

Alclometasone dipropionate

Fluocinolone acetonide

Desonide

Fluocinolone acetonide

Hydrocortisone Hydrocortisone Hydrocortisone Hydrocortisone Hydrocortisone Hydrocortisone

Reproduced with permission from: National Psoriasis Foundation, http:// www.psoriasis.org/NetCommunity/Page.aspx?pid=469.

Other, more unconventional therapies for COE include KTP/532 laser [28], tea tree oil (although it is unclear whether this study enrolled patients with acute otitis externa or COE, and resistance was found in Pseudomonas species) [29], a conchal flap meatoplasty [30], the Canter bury technique for canalplasty [31], intradermal injection of antibiotics and steroids [32 ], and chemical peel of the ear [33 ]. Future work may target proteases known to contribute to chronic inflammatory skin conditions. Proteases matrix metalloproteinases (MMPs) and human neutrophil elas tase (HNE) were found to be significantly higher in COE

Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

346 Otology and neuro-otology

ears than control ears; ilomastat and recombinant alpha 1 antitrypsin (rAAT) inhibited 60% of MMP and 98% of HNE activity. The authors speculate on the therapeutic potential of these protease inhibitors [34]. Finally, in a randomized, double-blind, placebo-controlled trial, bac teriophage (virus that infects and kills bacteria) therapy was well tolerated and effective, significantly improving patient symptom score and physician assessment com pared with placebo therapy for patients with COE due to antibiotic-resistant P. aeruginosa [35 ]. Conclusion Chronic otitis externa, a condition we share with our feline and canine friends, can be caused by many factors, with otorrhea, pruritis, discomfort, and fullness as the final common symptompathway. Treatment is aimed at remov ing all potential irritants to the skin of the canal, quelling the inflammation with medical management, reserving surgery for end-stage disease, and investigating the under lying source, whether exogenous (e.g. contact dermatitis) or endogenous (e.g. autoimmune/atopic). Frustrating for both patient and doctor, a ‘truce’ – stabilization and control of the disease process – is often the best we can hope for. Acknowledgements The author wishes to thank Dr Kenneth Greer, Division of Dermatology, Department of Internal Medicine, University of Virginia and Dr Prashant Raghavan, Department of Radiology, University of Virginia for the images used in this article. References and recommended reading Papers of particular interest, published within the annual period of review, have been highlighted as: of special interest of outstanding interest Additional references related to this topic can also be found in the Current World Literature section in this issue (p. 411). 1 Ali R, Burns P, Donnelly M. Otitis externa: quality of life assessment. Ir J Med Sci 2008; 177:221–223. 2 Toh A, De R. Spontaneous cerebrospinal fluid otorrhoea presenting as otitis externa. Eur Arch Oto-Rhino-Laryngol 2007; 264:689–691. 3 De Zoysa N, Vasani S, Kaniyur S, Frosh A. Gustatory otorrhoea: a rare case of congenital external ear salivary fistula. J Laryngol Otol 2009; 123:1371– 1374. Case report of a salivary fistula diagnosed by sending the otorrhea for amylase and treated by superficial parotidectomy. 4 Klemens JJ, Recant W, Baron JM, Saadia-Redleaf MI. Amyloidosis of the external auditory canal. Ear Nose Throat J 2010; 89:219–220. Case report; diagnosed by ear canal biopsy. 5 Lang EE, el Zaruk J, Colreavy MP, et al. An unusual case of external ear inflammation caused by sarcoidosis. Ear Nose Throat J 2003; 82:942–945. 6 Konttinen YT, Ramsay H, Hietanen J, et al. Otitis externa sicca/fibrotising external otitis (FEO) as a complication of Sjogren’s syndrome. Clin Experiment Rheumatol 2000; 18:746–748. 7 Illum P, Thorling K. Otological manifestations of Wegener’s granulomatosis. Laryngoscope 1982; 92 (7 Pt 1):801–804. The work was not funded. Conflicts of interest None declared.

8 Ghaffar SA, Todd PM. Chronic recurrent otitis externa secondary to allergic contact dermatitis to nickel and phosphorus sesquisulfide. Contact Derm 2009; 61:124–125. 9 Sood S, Strachan DR, Tsikoudas A, Stables GI. Allergic otitis externa. Clin Otolaryngol Allied Sci 2002; 27:233–236. 10 Yariktas M, Yildirim M, Doner F, et al. Allergic contact dermatitis prevalence in patients with eczematous external otitis. Asian Pac J Allergy Immunol 2004; 22:7–10. 11 Derebery J, Berliner KI. Foot and ear disease: the dermatophytid reaction in otology. Laryngoscope 1996; 106:181–186. 12 Yariktas M, Doner F, Dogru H, Demirci M. Asymptomatic food hypersensitivity prevalence in patients with eczematous external otitis. Am J Otolaryngol 2004; 25:1–4. 13 Lum CL, Jeyanthi S, Prepageran N, et al. Antibacterial and antifungal proper ties of human cerumen. J Laryngol Otol 2009; 123:375–378. In culture, human cerumen has potent antibacterial activity against S. aureus , P. aeruginosa , and C. albicans but not as potent against E. coli . 14 Pata YS, Ozturk C, Akbas Y, et al. Has cerumen a protective role in recurrent external otitis? Am J Otolaryngol 2003; 24:209–212. 15 Gray RF, Sharma A, Vowler SL. Relative humidity of the external auditory canal in normal and abnormal ears, and its pathogenic effect. Clin Otolaryngol 2005; 30:105–111. 16 Martinez Devesa P, Willis CM, Capper JW. External auditory canal pH in chronic otitis externa. Clin Otolaryngol Allied Sci 2003; 28:320–324. 17 Ho T, Vrabec JT, Yoo D, Coker NJ. Otomycosis: clinical features and treatment implications. Otolaryngol Head Neck Surg 2006; 135:787–791. 18 Vennewald I, Klemm E. Otomycosis: diagnosis and treatment. Clin Dermatol 2010; 28:202–211. Excellent review of antifungal agents for otomycosis with thorough yet concise tables. Article addresses the evidence regarding ototoxicity of antifungals as well. 19 Yenisehirli G, Bulut Y, Guven M, Gunday E. In vitro activities of fluconazole, itraconazole and voriconazole against otomycotic fungal pathogens. J Lar yngol Otol 2009; 123:978–981. Solid ‘translational’ study looking at in-vitro activity of antifungal agents against fungal isolates from 92 otomycosis patients. Interestingly, all Aspergillus isolates were resistant to fluconazole. Voriconazole was most potent. 20 Becker GD. Treatment of chronic otitis externa with trichophyton, oidiomy cetes, epidermophyton antigen. Otolaryngol Head Neck Surg 1980; 88: 293–294. 21 Hopsu E, Pitkaranta A. Idiopathic inflammatory medial meatal fibrotizing otitis presenting in children. Otol Neurotol 2008; 29:350–352. 22 Slattery WH 3rd, Saadat P. Postinflammatory medial canal fibrosis. Am J Otol 1997; 18:294–297. 23 Selesnick S, Nguyen TP, Eisenman DJ. Surgical treatment of acquired external auditory canal atresia. Am J Otol 1998; 19:123–130. 24 Becker BC, Tos M. Postinflammatory acquired atresia of the external auditory canal: treatment and results of surgery over 27 years. Laryngoscope 1998; 108:903–907. 25 Suzukawa K, Karino S, Yamasoba T. Surgical treatment of medial meatal fibrosis. Report of four cases. Auris Nasus Larynx 2007; 34:365–368. 26 Golder J. Oral steroids in the treatment of otitis externa. Aust Fam Physician 1999; 28:775. 27 Caffier PP, Harth W, Mayelzadeh B, et al. Tacrolimus: a new option in therapy-resistant chronic external otitis. Laryngoscope 2007; 117:1046– 1052. 28 Hughes RG, Courteney-Harris RG, Wilson PS. Longer term follow up for treatment of chronic otitis externa by KTP/532 laser. J Laryngol Otol 2001; 115:862. 29 Farnan TB, McCallum J, Awa A, et al. Tea tree oil: in vitro efficacy in otitis externa. J Laryngol Otol 2005; 119:198–201. 30 Kumar PJ, Smelt GJ. A long term follow up of conchal flap meatoplasty in chronic otitis externa. J Laryngol Otol 2007; 121:1–4. 31 Sharp HR, Oakley RJ, Padgham ND. The Canterbury technique for canalplasty via an endaural approach in the surgical management of chronic refractory otitis externa. J Laryngol Otol 2003; 117:195– 197. 32 Savastano M, Ferraro SM, Marioni G. Perichondritis with or without external otitis and intradermal injection: a new therapeutic approach. J Otolaryngol Head Neck Surg 2009; 38:568–572. A case series without long-term data presenting another method (intradermal) of delivering drug to the inflamed ear. Note: ‘flogosis’ means inflammation in Spanish.

Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

Assessment and management of chronic otitis externa Kesser 347

35 Wright A, Hawkins CH, Anggard EE, Harper DR. A controlled clinical trial of a therapeutic bacteriophage preparation in chronic otitis due to antibiotic resistant Pseudomonas aeruginosa : a preliminary report of efficacy. Clin Otolaryngol 2009; 34:349–357. An interesting, different, and potentially efficacious approach to treating COE with bacteriophages – viruses that kill bacteria. The article assumes bacterial infection underlies COE, which may not always be the case.

33 Fusconi M, Chiarini F, Taddei AR, et al. Chemical ear peeling: a simple technique for the treatment of chronic external otitis: how we do it. Clin Otolaryngol 2010; 35:424–429. A short ‘how to’ article without much data or long-term follow-up. Efficacy of this technique remains unproven. 34 Antonelli PJ, Schultz GS, Cantwell JS, et al. Inflammatory proteases in chronic otitis externa. Laryngoscope 2005; 115:651–654.

Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

Otology & Neurotology 39 :e1026–e1033 ! 2018, Otology & Neurotology, Inc.

Cholesteatoma of the External Auditory Canal: Review of Staging and Surgical Strategy

Udayabhanu HN, Sampath C. Prasad, Alessandra Russo, Golda Grinblat, and Mario Sanna

Department of Otology, Neurotology and Skull Base Surgery, Gruppo Otologico, Piacenza-Rome, Italy

reconstruction was done in 19 cases of stages I and II. Of 12 cases in stage III, 3 cases underwent canalplasty with reconstruction. Subtotal petrosectomy was done in five cases. Intact canal wall mastoidectomy with canalplasty in two cases and radical mastoidectomy in two cases. Fascia, cartilage, muscle, and bone dust were used for reconstruc tion. Median follow-up period was 6 years and no recurrence of cholesteatoma was observed. Conclusion: EACC is unique entity. Intraoperative and radio logical findings assist in correct and practical staging of EACC. Late stage presentations of EACC are common. Definitive surgical treatment in our series avoided recurrence of cholestea toma. Key Words: Canalplasty — Cholesteatoma — External auditory canal — Subtotal petrosectomy. staging does not correspond to clinical findings or surgi cal management. The objective of the present series which is one of the largest in the literature was to elucidate causes and presentation of EACCs, review the existing staging system, and suggest the surgical strategies for definite treatment. Our center is a quaternary referral center for otology and lateral skull base surgeries. A retrospective chart-review of all patients operated at our center from 1983 to 2017 for all cholesteatomas were conducted and only patients with EACCs were included in this study. At our center, EACCs are defined by the presence of cholesteatoma distinctly arising from the EAC without evidence of origin from any other sites in the middle ear or mastoid. The inclusion criteria used to select patients were: 1) patients with EACCs, 2) patients with a minimum follow-up of at least 12 months. The exclusion criteria were: 1) patients with any other type of middle ear, mastoid, or petrous choles teatomas, 2) patients with incomplete case records, follow-up of less than 1 year or those lost to follow-up. This yielded 31 cases for analysis. The data extracted from the case sheets included demographics, laterality, clinical presentation, etiol ogy, past surgeries, intraoperative findings, complications, recurrences, revision-surgeries, preoperative audiometric data, and follow-up. PATIENTS AND METHODS Otol Neurotol 39: e1026–e1033, 2018.

Introduction: External auditory canal cholesteatomas (EACC) is insidious in nature and rare entity. There are only few case series on EACCs and surgical strategy is not standardized. Objectives: 1) To elucidate etiology of EACC and cardinal features. 2) To suggest a practical staging of EACC. 3) To enumerate surgical management according to stage of EACC. Study Design: Retrospective study in a quaternary referral center of 31 consecutive cases of EACC. Results: Thirty-one patients with EACC were reviewed. Unilateral otorrhea 19 (61.2%), hearing loss 22 (70.9%), and otalgia 8 (25.8%) are cardinal symptoms. Sixteen primary and 15 secondary EACCs were treated. Bone erosion was observed in 20 cases. In the present series, stage III ¼ 12 (38.7%), stage II ¼ 8 (25.8%), stage I ¼ 11 (35.4%) under went definitive treatment by surgery. Canalplasty with External auditory canal (EAC) is a unique cul-de-sac in the human body which requires undisturbed self cleansing to keep it patent (1). Any factor that affects patency of EAC may lead to EACC formation. EACCs are broadly divided into primary and secondary (2–4). While primary external auditory canal cholesteatomas (EACCs) are generally idiopathic, secondary cholestea tomas can be congenital, posttraumatic, postoperative, or postinflammatory. EACC rarely presents to a busy otol ogy clinic with an estimated incidence of 1:1,000 of all newly diagnosed patients (1). Although originally described by Toynbee in 1850, it was only in the late 20th century that reliable separation from other EAC pathologies like keratosis obturans was possible (5,6). EACCs may be difficult to distinguish from the com mon otitis externa, especially in its early stages, due to the fact that otalgia in EACC gradually disappears with disease progression (7). Naim et al. (8) proposed a staging that was based on rare histologic findings which has been often used in the literature. However, this

Address correspondence and reprint requests to Udayabhanu HN, M.S., Gruppo Otologico, C/o Casa di Cura, Via Emmanueli 42, Piacenza 29121, Italy, E-mail: udayaentskullbase@gmail.com

The authors disclose no conflicts of interest. DOI: 10.1097/MAO.0000000000001972

e1026

Copyright © 2018 Otology & Neurotology, Inc. Unauthorized reproduction of this article is prohibited.

CHOLESTEATOMA OF THE EXTERNAL AUDITORY CANAL

e1027

TABLE 1. Patient and EAC cholesteatoma characteristics

The preoperative audiological data, including pure-tone average (average of 0.5–1–2–4 kHz) of bone conduction, air conduction, and air-bone gap (ABG), according to the Sanna et al. (9) classification of hearing were noted and analyzed. All patients underwent complete preoperative oto-neurologic eval uation, including preoperative otoendoscopy. Preoperative and postoperative facial nerve (FN) function was graded by the House-Brackmann) grading system (10). A high-resolution computed tomography scan of the tempo ral-bone was obtained in all patients. We devised staging based on intraoperative and radiological findings. Our patients were divided into three stages based on radiological evaluation determining the presence or absence of bone erosion, extent of the disease and involvement of surrounding structures. This was also confirmed intraoperatively. Surgeries adopted in this series included: 1) Canalplasty with or without reconstruction, 2) Intact canal wall mastoidectomy with canalplasty, 3) Radical mastoidectomy, 4) Subtotal petrosectomy. These procedures are described elsewhere (11). Operative notes were analyzed for location, bone erosion and extent of disease, surgical technique used and reconstruction methods (Table 1). Review of the Literature A PubMed search was performed using appropriate search words between 2000 till date. All case series with over 10 cases of EACCs were included in the review. The etiology, clinical features, surgical technique, graft materials, complication, recurrence, and revision rates with follow-up time were tabu lated and compared. The present study was approved by the Institutional Review Board of Casa Di Cura, Piacenza, Italy for ethical research (Table 2). Of the 7020 cases of cholesteatomas operated in our center from 1983 to 2017, 31 patients with EACCs were analyzed. The incidence was around four per thousand temporal bone cholesteatomas and one per thousand for all otological/lateral skull base, in patients operated at our center. Demography and Etiology The mean age of the study population was 41.2 years, range (6–75 yr) with male:female ratio of 1:1.63, 15 (48.3%) were right ears and 16 (51.6%) were left ears. Sixteen (51.6%) cases were primary and 15 (48.3%) cases were secondary EACCs. Among the 15 secondary EACCs, poststenotic 4 (26.6%) and postoperative 4 (26.6%) were the most common etiology. Followed by posttraumatic 3 (20%), posttumorous 3 (20%), and post inflammatory 1 (6.6%) cases. Clinical Features Of the 31 patients, 22 (73%) had hypoacusis, followed by otorrhea 19 (63%) otalgia 8 (27%). Six (20%) of patients had complaints of chronic itching in the ear and about 5 (17%) of the study group had dizziness/vertigo. Two (6.4%) of the patients among 31 had anacusis. Audiological Analysis Of the 22 cases with hearing loss was more common in secondary EACCs 12 (54.5%) when compared with RESULTS

Patient and Cholesteatoma Characteristics

n (%)

Demography Patients

31 (100)

Mean age (yr) Male: female

41.2

12:19

Unilateral: bilateral

31:0

Incidence among temporal bone cholesteatomas Incidence among otology/lateral skull base cases

4/1,000 1/1,000

Etiology

Primary (Idiopathic)

16 (51.6) 15 (48.3) 4 (26.6) 4 (26.6)

Secondary

Stenosis

Postoperative Posttraumatic Posttumorous

3 (20) 3 (20) 1 (6.6)

Postinflammatory

Clinical features Hearing loss

22 (70.9) 19 (61.2) 8 (25.8) 6 (19.3) 5 (16.1)

Otorrhoea

Otalgia

Chronic itching ear Dizziness/vertigo

Anacusis

2 (6.4)

Intraoperative signs and structures involved Bone erosion

20 (64.5) 7 (22.5) 5 (16.1)

Temporomandibular joint exposed

Facial nerve exposed

Dura exposed

2 (6.4) 2 (6.4) 1 (3.2) 1 (3.2)

Lateral semicircular canal fistula

Jugular bulb exposure

Meningoencephalic herniation

Stage classification I

11 (35.4) 8 (25.8) 12 (38.7) 16 (51.6) 7 (22.5) 4 (12.9)

II

III

Location

Inferior Posterior Anterior Superior

2 (6.4) 2 (6.4) 2 (6.4)

Circumferential

Middle ear extension

Surgical approaches Canalplasty

20 (64.5) 2 (6.4) 2 (6.4) 2 (6.4) 5 (16.1)

Canalplasty þ myringoplasty Canalplasty þ mastoidectomy Radical mastoidectomy Follow-up Median follow-up period Recurrence of cholesteatoma Tympanic membrane reperforation Subtotal petrosectomy

6 yr

0 (0)

3 (9.7)

primary cases 9 (40.9%). Of these, two patients with anacusis and five cases of subtotal petrosectomy (STP) were excluded. Audiological analysis was done for ABG. The pre and postoperative mean ABGs in primary EACCs were 28.75 dB and 6.87 dB respectively ( p < 0.0019). Similarly among secondary EACCs, the

Otology & Neurotology, Vol. 39, No. 10, 2018

Copyright © 2018 Otology & Neurotology, Inc. Unauthorized reproduction of this article is prohibited.

e1028

H. N. UDAYABHANU ET AL.

NA NA NA NA HL more common in 2 8 EACC. (0.6) (2) ME (3) MAS (1)

(n) Special points

Mentions HA, cerumen, Cotton tip use as risk factors for 1 8 EACC.

Spontaneous EACC managed by aural toilet.

radiologic findings. Definitive treatment strategy.

ME (5) MAS (4) TT (1) NA Aural toilet in Spontaneous EACC.BE was found in all cases. FN (1)

Surgical exploration for correct staging. 1 8 EACCs had more tobacco consumption.

NA 1 8 EACC in 48% reported mechanical trauma (30)

Conservative treatment for post radiotherapy EACCs.

Early intervention avoids recurrence

Concept of multilayered reconstruction

Simple practical staging based on surgical &

0-1-12-1-0 NA NA (17) (4) NA MAS (1) NA Histopathologic Staging TMJ (11) MAS (8) M E (3) (n ¼ 30)

NA Radiological staging

(A þ I) (39) NA NA (25) (NA) (0) NA NA

(28)

(10)

Meatoplasty

Adjacent

TMJ (14) ME (8)

involved (n)

Dura (2)

LSCC (1)

FN (2)

FN (2)

MAS (14)

TMJ (2)

MCF (1)

MAS (7)

FN (5)

TMJ (7) JB (1)

Dura (2)

MEH (1)

LSCC (2) ME (2)

Structures

Recurrence (n)

(15) (0)

41-47-45-2-0 NA CP þ R (44) (2) (2) 1 8 EACC Preop (1) (0)

(1.8) (1)

(6) (0)

Follow-up (yr)

(median)

NA CP þ MP (10) CWD þ OB

CP þ TP (3)

CP þ MT (10)

CP þ M P (2)

CP þ MT (2)

Surgery

Type (n)

CWD (11) NA (42)

5-8-8-0-2 NA CP CWD (13)

CP (14)

CP (4)

TC (6)

MCFA (2)

(19)

CP (20)

RP (2)

STP (5)

Air-bone Gap

1 8 40.9%

2 8 59.09%

1 8 6.87dB

2 8 10dB

TABLE 2. Review of the literature of EAC cholesteatoma EACC location

> 20 dB (27%) Postop NA NA

Pre-op

28.75dB

42.85dB

Post-op

1 8 EACC

0-32-0-0-0 2 8 EACC

4-14-5-0-0 2 8 EACC

10-5-0-0-0

10-20-17-10-0 NA 14-8-7-0-0

11-12-13-1-0

4-16-7-2-2

(A-I-P-S-C)(n)

Symptoms n (%)

Signs and

Or 4 (10.2)

Ot 5 (12.8)

Pr 7 (17.9)

Or 6 (46.1)

Ot 3 (9.6)

HL 4 (12.9)

BE 13 (100)

Or 12 (70.5)

Ot 3 (17.6)

HL 4 (23.5) Or 6 (13)

Ot 18 (38)

HL 5 (10)

Pr 10 (21)

Or 28 (62.2)

Ot 23 (51.1)

Or 12 (41)

Ot 17 (59)

HL 17 (59)

Or 22 (65)

Ot 4 (12)

HL8 (27)

BE 34 (100)

Or 28 (100)

Pr 28 (100) Ot 2 (7)

Or 19 (61.2)

Ot 8 (25.8)

HL 22 (70.9) Pr 6 (19.3)

Ve 5 (16.1)

BE 20 (64.5)

(5)

(0)

(0)

(3)

Lin et al., 2009 (45) 34/11 (7)

(0)

(1)

(1)

(0)

1 8 indicates primary EACC; 2 8 , secondary EACC; A-I-P-S-C, anterior-inferior-posterior-superior circumferential; BE, bone erosion; Bil, bilateral; CP, canalplasty; CWD, canal wall-down mastoidectomy; EACC, external auditory canal cholesteatoma; FN, facial nerve; HA, hearing aids; HL, hearing loss; JB, jugular bulb; LSCC, lateral semicircular canal; MCFA, middle cranial fossa approach; ME, middle ear; MEH, meningo encephalic herniation; MP, myringoplasty; NA, not available; OB, obliteration; Or, otorrhea; Ot, otalgia; Pr, prurigo; R, reconstruction; RP, radical petrosectomy; STP, subtotal petrosectomy; TMJ, temporomandibular joint; Ve, vertigo.

1 8 /2 8 EACC Bil (n) (39) 13/26

Patients (n)

8/5

17/0

25/23

(29)

14/15

13/22

(28)

22/6

(31)

16/15

Naim et al., 2005 (17)

Case series

Vrabec et al., 2000

Heilbrun et al., 2003 (13)

Owen et al., 2006 (48)

Shin et al., 2010

Dubach et al., 2008 (34)

Konishi et al., 2016

Present series

Otology & Neurotology, Vol. 39, No. 10, 2018

Copyright © 2018 Otology & Neurotology, Inc. Unauthorized reproduction of this article is prohibited.

CHOLESTEATOMA OF THE EXTERNAL AUDITORY CANAL

e1029

FIG. 1. Stage-wise location of EACC. EACC indicates external auditory canal cholesteatoma. [From left to right in this figure: image 1(R), image 2(L), image 3(L), image 4(L), image 5(R). R, right ear; L, left ear].

pre and postoperative mean ABGs were 42.85 db and 10 db respectively ( p < 0.006).

Follow-up and Recurrence The median follow-up period in our study is 6 years and none of the 31 cases had recurrence after definitive surgical treatment. Tympanic membrane reperforation in anteroinferior quadrant observed in 3 of 31 cases was corrected later by myringoplasty. Scholefield (12) introduced the term EACC in 1893 but the precise definition was given by Piepergerdes et al. (6), in 1980. The incidence of EACCs is 1.2 to 7.1 cases per 1,000 new otologic patients per year (13,14). In our center the incidence is 1 case per 1,000 new otologic in patients or 4 per 1,000 cases of temporal bone choles teatomas (15–17). Etiopathogenesis of EACC The pathogenesis of spontaneous ear canal cholestea toma is attributed to factors like 1) microtrauma to the external canal skin; 2) retention of hard or adulterated cerumen; 3) focal osteitis; 4) hypoxia leading to angio genesis via scatter factor, tyrosine-kinase c-Met recep tor, and vascular endothelial growth factor; and 5) decreased epithelial migration secondary to aging; or 6) erratic keratin deposition and poor blood supply in the floor of EAC (4,8,18,19). The differential migration velocity theory of the canal epithelium between healthy and EACC ears has been refuted by Makino and Amatsu (20). The enhanced expression of mind bomb 1 anti body-positive proliferating cells, transforming growth factor-alpha, and epidermal growth factor receptor in the basal and suprabasal layers of the epithelium in choles teatomas has been found (18). Bonding et al. (21), and Hickey et al. (22), were able to associate idiopathic EACC with congenital anomalies like a rudiment of the first branchial cleft (23). Chronic use of cotton tipped applicators has been described as a potential risk factor but whether this is a cause or occurs as an epiphenomenon attributable to ottorhea remains an open question. In contrast secondary EACCs are due to obstruction (auditory canal stenoses, exostoses, myce tomas) or defects of the EAC affecting the mastoid cell DISCUSSION

Intraoperative Findings Review of the operation records showed that 20 (64.5%) of the cases had bone erosion. Temporo-man dibular joint (TMJ) was the most common surrounding structure exposed due to bone erosion in seven (22.5%) cases, followed by FN in five (16.1%), dura two (6.4%), lateral semicircular canal fistula in two (6.4%), menin goencephalic herniation in one (3.2%), and jugular bulb exposure in one (3.2%) (Table 1). Location and Extensions Among 31 cases of EACC, 16 (51.6%) cases were located in the floor of EAC. Seven (22.5%) cases were located in posterior wall and four (12.9%) cases in the anterior wall of EAC causing TMJ erosion. Two (6.4%) cases had involvement of superior and attic wall. Cir cumferential extension and location of cholesteatoma was seen in two (6.4%) of cases. About two (6.4%) of the study group had EACCs extending into the middle ear. The location and extension of the EACCs has been depicted in Figure 1. Staging Among 31 patients in our study group, 11 (35.5%) cases without bone erosion were classified as stage I. Eight (25.8%) cases that had bone erosion but no involve ment of adjacent structures were staged as II and 12 (38.7%) cases that had bone erosion with involvement of adjacent structures but no complications were stage IIIA. None of our patients had a stage IIIB disease (Fig. 2). Surgical Results Most of our patients presented with advanced stages of EACCs according to our classification. Canalplasty was performed in 20 (64.5%) of cases, canalplasty with myringoplasty in 2 (6.4%), and canalplasty with mastoidectomy in 2 (6.4%) of the cases. Subtotal petrosectomy was done in five (16.1%) and radical mastoidectomy with reconstruction in two (6.4%) of cases.

Otology & Neurotology, Vol. 39, No. 10, 2018

Copyright © 2018 Otology & Neurotology, Inc. Unauthorized reproduction of this article is prohibited.