Medical Management of End-Stage Canine Otitis Externa

Jan A. Hall, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada

Introduction
Otitis Externa is one of the most common clinical presentations in small animal practice, representing 10-20% of canine cases and up to 15% of a small animal clinic caseload. Not only can otitis externa be the source of severe discomfort for the animal, and frustration for the veterinarian treating the case, but also a poor response to therapy is frequently the source of significant client dissatisfaction.

Medical management of canine otitis externa should be aggressive enough to avoid the development of chronic pathological changes and focus on both the control of the clinical signs as well as identification of the underlying trigger factors involved. The initial aim of therapy should be to reduce inflammation within the ear canal, as this will provide comfort for the patient and may significantly decrease secondary organism involvement.

If medical treatment is unsuccessful, and the condition progresses to the chronic stage, the associated inflammation results in significant pathologic change. Epidermal and glandular hyperplasia leads to thickening of the ear canal wall with resultant narrowing and eventual total obliteration of the ear canal. This impedes ear examination and medical treatment. Calcification of the auricular cartilages may further increase the pain experienced. Furthermore, in chronic cases, deafness and other neurological abnormalities may develop, complicating the clinical picture. The term 'obstructive' or 'end-stage' ear disease is used to describe ear canals that have reached the point where practitioners believe that medical therapy can no longer be of benefit, regardless of the underlying etiology. At this point, surgical intervention with a total ear canal ablation with lateral bull osteotomy (TECA-LBO) is often recommended.

TECA-LBO is a technically difficult procedure with a high risk of post-operative complications (12-82% depending on study), including wound dehiscence, infection, facial nerve paralysis, chronic fistulous tract formation and deafness. Medical therapy should be considered as an alternative, especially in those cases where ear disease is associated with general dermatologic disease. The object of medical therapy is not necessarily to reverse the pathologic changes completely, but to halt progression and maintain the patient with a degree of comfort.

The pathogenesis of otitix externa
Otitis externa is best considered to be a multifactorial problem with predisposing, primary and perpetuating factors that interact to produce clinical disease. Complete resolution of an ear problem is very unlikely unless underlying trigger factors are identified and controlled.

Predisposing factors- increase the risk of development of otitis externa, e.g. conformation (congenital stenosis - Shar-Pei; excessive hair - poodles), lifestyle (grooming, swimming, excessive ear care), obstructive lesions (neoplasms, polyps), systemic disease (pyrexia, immune suppression, viruses, debilitation).

Primary factors - incite the condition, e.g. foreign bodies, hypersensitivity disorders (atopy, adverse food reactions, drug reaction), immune-mediated (pemphigus complex), parasites (Otodectes), DermaBenSs disorders (idiopathic seborrhea), glandular disorders (excessive cerumen/sebum accumulation, sebaceous adenitis).

Perpetuating factors - prevent the resolution of the problem, e.g. organism overgrowth (bacteria, yeast), pathological change (epidermal/glandular hyperplasia, stenosis, calcification, otitis media), over-treatment with topical ear medications.

Although obstructive ear disease may be associated with many different underlying etiologies (including allergy and bacterial infection), specific breed related associations have also been noted. Cocker spaniels, in particular, are over-represented in many otitis externa studies and are also the most common breed to develop obstructive or end-stage ear disease. It was originally hypothesized that because of poor air circulation and increased humidity, the pendulous nature of the ears mad the breed more prone to otitis externa. However, it is more likely that the high incidence of the condition in the Cocker spaniel is associated with the breed predisposition for disorders of keratinization, and associated ceruminous otitis externa.

Many dogs with primary idiopathic seborrhea produce and oily, yellow-cream secretion that on ear canal cytology contains large numbers of epidermal cells as well as cerumen. This secretion, without ear canal cytology, may be mistaken for purulent material, leading to inappropriate use of antimicrobial preparations.

The term 'Idiopathic proliferative (inflammatory/hyperplastic) otitis externa of the Cocker spaniel' has been used to describe ceruminous otitis externa that appears to rapidly progress the the end-stage, where the ear canal may be totally obliterated by hyperplastic tissue. It has been suggested that changes in fatty acids within the cerumen of affected dogs stimulates an enhanced inflammatory response.

The pathology of canine otitis externa|
Although there are many different factors involved in the development of otitis externa, the clinical progression of the condition and ultimate endpoint may be strikingly similar regardless of the original etiology.

In the early stages of otitis externa, inflammation produces erythema and edema of the ear canal wall. As the condition becomes more chronic, the inflamed canal wall becomes hyperplastic. Histologically, epidermal acanthosis with mild to moderate jyperkeratosis, ceruminous gland hyperplasia, ceruminous gland ectasia and sebaceous gland hyperplasia are noted with a mixed inflammatory infiltrate consisting of lymphocytes, mast cells and polymorphonuclear cells. The dramatic histologic changes may permanently alter the microclimate within the canal, promoting colonization by opportunistic microorganisms that may produce further inflammation in their own right. As the inflammation progresses, dermal fibrosis followed by calcification of the auditory cartilages and osseous metaplasia may be noted. This leads to decreased flexibility within the ear canal, progressive stenosis and finally obstructive ear disease.

The approach to the end-stage ear
Evaluation of the end-stage ear is no different from the approach to the regular otitis externa case, although examination if the canal may be severely hampered by stenosi. Clinical assessment is bases on a thorough history, covering how often the pet is bothering the ear (number of times per hour or day, extent of ear rubbing or head shaking, etc.), clinical examination findings , ear canal cytology and the results of bacterial culture, if indicated.

Potential predisposing or primary factors (e.g. ear care, exposure to water, general health, parasites, etc. ) should also be explored. A full dermatological exam is included as part of the evaluation. The potential for a generalized hypersensitivity disorder and primary idiopathic seborrhea should be addressed.

The canal is assessed for evidence of ulceration, extent of hyperplasia or discharge/debris using a transilluminator or otoscope. The canal is examined for evidence of ulceration, hyperplasia or discharge/debris. Visualization of the tympanic membrane is usually impossible in the end-stage case.

Ear canal cytology is performed by taking a sample from the vertical canal-horizontal canal junction using a Q-tip. After heat fixing and staining with Diff-Quik, the slide is examined under high power dry field (x40) or oil immersion (x100). The number of organisms and/or inflammatory cells should be determined at each visit. The results must be interpreted in the light of the history and clinical findings. Cytology should be repeated at every re-evaluation (normally every two weeks during the treatment phase).

Current texts suggest that greater than 5 Malassezia and 25 bacteria per high power dry field (x40) are abnormal in dogs. Because of the extensive pathologic change noted in the end-stage ear canal, colonization with microorganisms is not unusual. The presence of organisms is not synonymous with infection. If bacteria or yeast are noted within the cerumen or on epithelial cells, but there are few inflammatory cells presen, this is indicative of colonization, not infection.

If suspicious bacteria or large numbers of inflammatory cells are noted, the author will perform a bacterial culture. However, while waiting for culture results, anti-inflammatory therapy alone is instituted, not antibiotics. Antibiotic therapy is only instituted if indicated by a poor clinical and cytological response at subsequent re-evaluations. The goal is to encourage the ear canals to 'self-cure', thereby minimizing the development of resistant infections. Since adopting this strategy, the author's use of topical antibiotics has dropped precipitously.

Bacterial culture is performed when inflammatory cells or large numbers of bacteria are noted on ear cytology. The results of bacterial culture and sensitivity and minimum inhibitory concentration (MIC) measurement may be used to determine the best systemic antibiotic choice; however, recent research suggests that systemic antibiotic therapy is not helpful in the treatment of otitis externa, and may contribute to colonization by resistant organisms. Radiography or computed tomography (CT) may be useful to diagnose middle ear involvement if suspected on clinical examination. Radiographs can also be used to confirm the presence of calcification of the auricular cartilages in chronic cases, although this is not usually necessary. The author does not routinely perform inaging on end-stage ear cases where medical therapy will be instituted.

Treatment options for end-stage otitis externa
Despite the severity of the end-stage ear canal, many cases will respond favorably to medical treatment if it is instituted aggressively. It is important not to lose sight of the need to identify predisposing and primary factors. As in the treatment of any otitis externa case, the aim of therapy should be to reduce inflammation within the ear canal. This will provide comfort for the patient and may significantly decrease secondary organism involvement by producing a microenvironment that no longer favors the growth of the organism. The goal in medically treating end-stage dogs is to control the clinical disease and stop progression, not necessarily to reverse the pathological changes.

Glucocorticoids
Glucocorticoids, either topically or systemically, benefit by reducing inflammation and proliferative changes within the end-stage ear canal. Glucocorticoids will have a profound effect on cytokine production. This results in decreased inflammation, pruritus and pain. Glucocorticoids will also decrease the production of cerumen and sebum, counteracting the effects of ceruminous and sebaceous hyperplasia. They will also decrease epidermal hyperplasia and hyperkeratosis of the ear canal.

Topical glucocorticoids that are not in combination with antimicrobial agents are preferred because they decrease the risk of altering the microenvironment in the ear canal. The excessive use of antimicrobial agents will lead to colonization by multiresistant organisms.

A variety of topical corticosteroids have been recommended, including flucinolone, betamethasone and dexamethasone. The author has found 1% hydrocortisone combined with an astringent, 2% Burow's solution (aluminum acetate) in propylene glycol, to be very helpful in decreasing inflammation and drying the ear canals in many cases of otitis externa. These drops will produce a favourable response even in the face of apparent bacterial colonization or infection. The author uses this preparation as first line otitis externa therapy. Typical does are 2-3 drops for small dogs and 4-6 drops for large dogs q 12h. Weaning down to an as-needed basis based on a favorable clinical response is possible.

Systemic glucocorticoids at anti-inflammatory does (prednisone orally at 1-2 mg/kg/day) may be used to rapidly decrease inflammation, to combat the proliferative response and to control pain before weaning down to maintenance levels. Glucocorticoids have also been shown to aid in the elimination of resistant Pseudomonas strains through changes in the microclimate that no longer favor the growth of the bacteria. Glucocorticoid therapy is also recommended where large numbers of inflammatory cells (predominantly neutrophils) are noted on cytology.

Anecdotally, favourable results have been reported from the direct injection of glucocorticoids into proliferative tissue, after cleaning. Triamcinolone acetonide at 2 mg/mL has been injected at 0.1 mL does into proliferative lesions using a 22G needle (Rosychuk, WSAVA 2002).

Cyclosporin
Cyclosporin is a potent immunomodulatory drug with effects on T-cell activity. In humans, it has been used in organ transplantation and in the treatment of a variety of immune mediated and dermatologic diseases. In canine dermatology, it has been used for the treatment of perianal fistulae and other immune-mediated diseases. It has recently been approved for the treatment of canine atopic dermatitis.

In a pilot study, five client-owned dogs were treated with oral cyclosporine at 5 mg/kg twice daily for a minimum period of 12 weeks (Hall AAVD/ACVD 2003). All dogs were re-evaluated clinically every four weeks to monitor progress. All five cases showed significant clinical improvement based on owner and clinical assessments. Individual owners also commented on improved disposition, hearing and quality of life. Although bacterial colonization was noted on ear cytology, adjunctive ear medication were not required. A placebo-controlled study is proceeding.

Antibiotic therapy
There are many topical proprietary products containing combinations of antibiotics such as neomycin, gentamicin, polymixin B, and enrofloxacin with anti-fungal agents and/or corticosteroids. Typically, the product is administered on a twice-daily basis for the first week, then once daily for the second week pending a re-evaluation to ensure that the treatemen has been effective. Cytology should be used to assess response to therapy. As many products contain corticosteroids, clinical improvement should not necessarily be assumed to be associated with the antibiotic component (s).

Overuse of topical antibiotics must be discouraged as they may exacerbate otitis problems by encouraging colonization by resistant bacterial strains, in particular Pseudomonas aeruginosa, a ubiquitous organism in the environment, and Proteus mirabilis. Overuse of topical products may also lead to excessive maceration of the ear canal, or a contact allergic or irritant reaction.

Although the literature suggests that systemic fluoroquinolones may be beneficial, recent MIC research suggest that they may not be as helpful as first thought, even at the top of their flexible dose range. They may also encourage the overgrowth of resistant strains of bacteria, in particular Pseudomonas aeruginosa.

Antifungal therapy
Although any of the topical antimicrobial combination products containing an antifungal should be effective, because of the risk of colonization by multi-resistant bacteria, you should consider carefully whether antimicrobial treatment is warranted.

Oral antifungals, such as ketaconazole 5-10 mg/kg q 12-124h, itraconazole 5 mg/kg q 24h, or fluconazole 5-10 mg q 24h for 2-4 weeks, appear to work very well in severe infections or where topical therapy has not controlled the problem. Because of concerns regarding liver toxicity when using ketaconazole, blood work should be monitored.

Ear Flushing
Flushing the ear canal can be very effective in removing cerumen and debris to allow topical products to reach the canal wall. Removal of bacterial toxins, degenerative cellular debris and free fatty acids decreases the stimulation for further inflammation. Purulent material and inflammatory debris will inactivate some medications (e.g. polymixin B).

Flushing should never be attempted in the face of severe inflammation, as it may lead to erosion and ulceration of the ear canal. In acute ears, it is preferable to treat appropriately based on cytology then re-evaluate. Typically, the author will not recommend flushing the affected canal until satisfied that the inflammation is under control.

Ear flushing can be challenging in the end stage ear case because of the limited size of the ear canal. However, flushing debris from the ear canal can be of benefit when treating chronic Pseudomonas or Malassezia.

A warm solution of white vinegar in water (1 part of white vinegar to 3-5 parts water) makes an excellent general flush if well tolerated. This solution appears to be safe in the presence of a ruptured tympanum. Vinegar and water flushing is normally carried out every 2-3 days during the treatment protocol.

A proprietary ear flush with an acidic pH may also be useful. The author currently uses a 2% acetic acid, 2% boric acid cleanser (MalAcetic, DermaPet) when required for maintenance in dogs with chronic bacterial or Malassezia colonization. In-depth flushing under general anesthesia is not always that useful or practical in the end-stage case because of sever ear canal stenosis. A wipe impregnated with 2% acetic acid and 2% boric acid (MalAcetic Wet Wipes) may be used to clean the orifice area in those individuals with severe stenosis. Burow's solution may be used for the same purpose.

The surfactant product, Tris-EDTA, may significantly increase the sensitivity of Pseudomonas to topical gentamicin and the other aminoglycosides. The EDTA has a direct effect on the organism by chelating metal ions, thereby destabilizing the cell wall. Tromethamine (Tris) enhances the effect of the EDTA on the organism. Tris-EDTA solution is available as TrizEDTA from DermaPet in North America. The recommended protocol is to flush the canal 15 minutes prior to topical antibiotic use.