Aspergillus Otomycosis

Otomycosis is subacute or chronic superficial fungal infection of the external auditory canal and auricle. It is the most frequently encountered fungal infection in ear, nose and throat clinics. The organisms responsible for this clinical entity are usually environmental saprotrophic fungi especially A. niger. The fungi are usually secondary invaders of tissue already rendered susceptible by bacterial infections, physical injury or excessive accumulation of cerumen in the external auditory canal. Sometimes it is merely non-pathogenic fungal colonization of the external auditory canal.

 

Historical Perspective
Andral and Gavarret in 1843 and Mayer in 1844 first described fungal infections of the external auditory canal and subsequently Virchow suggested the term ‘otomycosis’. In 1851, Pacini was the first to describe a preparation for the treatment of otomycosis (cited by Tom, 2000). Additional reports were published at the beginning of the twentieth century (Galloway, 1903; Cheatle, 1920). Wolf described the relationship of various fungi to this clinical entity (Wolf, 1947). It was postulated that cleansing and drying were essential aspects of the management and provided symptomatic relief but whether additional therapy was necessary remained controversial. Gregson et al realised the significance of fungal infections in the aetiology of the otitis externa and labeled it as a neglected disease (Gregson et al, 1961).


The predominant role of A. niger in otomycosis was established in the 1960’s and 1970’s (Damato et al, 1964; Bezjak, 1970). Damato also believed that recurrence was likely if cleansing and drying were the only management regimes and further stated the role of tolnaftate in its treatment (Damato, 1966 & 1973). Stern et al suggested that most cases of otomycosis would resolve with meticulous cleansing and drying (Stern et al, 1988). Otomycosis classically has been described as a fungal infection of the external auditory canal but Paulose et al suggested that the term should be expanded and redefined to include fungal infections of the middle ear and open mastoid cavities (Paulose et al, 1989). Malignant (invasive) otitis externa, the most severe form of disease, was first described by Chandler (Chandler, 1968). Haruna et al updated the histopathological findings of otomycosis (Harunaet al, 1994), which were further elaborated by Vennewald et al (2002).

Epidemiology
Otitis externa is common and manifests as an acute or chronic form. The acute form affects four in 1,000 persons annually and the chronic form affects 3-5% of the population. Acute disease commonly results from bacterial (90%) or fungal (10%) overgrowth in an ear canal subjected to excess moisture or to local trauma (Osguthorpe et al, 2006).

Fungi have been implicated overall in ~9% of cases of external otitis. In various studies, it is estimated that about 5-25% of total cases of otitis externa are due to otomycosis (Del Palacioet al, 1993). The disease is worldwide in distribution. Otomycosis is more prevalent in warm, humid climates, particularly in the rainy season as compared to arid or cold climates. It is more frequent in individuals of lower socio-economic status with poor hygienic conditions. It is most commonly seen between 2nd and 3rd decades of life. Workers in mouldy or dusty settings are usually more affected. The prevalence of otomycosis is higher in malnourished children as compared to the normal children (Enweani et al, 1997).

There are many local predisposing factors of otomycosis such as chronic infection of the ear, use of oils, ear-drops, steroids, swimming and evidence of fungal infection elsewhere such as vaginitis or onychomycosis, etc. Local lesions observed in bacterial otitis create favourable conditions for the growth of fungi in the external and middle ear, as well as in post-operative cavities, especially in cases of open-type surgery. Persistent wetness of the external auditory canal predisposes to fungal infection.

Physicians need to have a high level of suspicion of otomycosis as a cause of persistent otorrhea, especially following treatment with topical antibiotic drops. Ofloxacin remains an excellent choice for bacterial otorrhea but it appears to increase the incidence of otomycosis (Jackman et al, 2005). There has been an increase in the prevalence of otomycosis in recent years possibly linked to the extensive use of antibacterial eardrops.

Mycology
In about 75% cases of otomycosis, Aspergillus genus alone is the causative agent. A. niger is the most common cause, with occasional cases caused by A. flavus and A. fumigatus (Than et al, 1980; Mugliston et al, 1985; Paulose et al, 1989; Lucente, 1993). In another study,Aspergillus was the predominant genus of fungi isolated from cases of otomycosis comprising 92% with A. niger implicated in 71% of the total isolated fungi (Yehia et al, 1990).

Clinical Features
Otomycosis usually presents with a history of itching, irritation, discomfort, pain and scanty discharge from the affected ear. There is also a feeling of blockage in the ear due to collection of debris material in external auditory canal. Irritation is more marked in fungal as compared to bacterial otitis externa.

Pruritus and discharge are the most common symptoms, with reddened epidermis and lining of the tympanic cavity being common (Kurnatowski et al, 2001). These manifestations are usually unilateral but rarely bilateral involvement has also been seen. If there is a concurrent perforation of the tympanic membrane and particularly otalgia is a prominent feature, suppurative otitis media caused by Aspergillus or other fungi should be considered (Tiwari et al, 1995; Ibekwe et al, 1997). Fungal infection should be suspected in all cases of chronic otitis externa which do not respond to conventional topical antibacterial therapy.

Otoscopic examination reveals infection confined to the ear canal. There is greenish or black fuzzy growth on cerumen or debris resembling wet ‘blotting paper’, which may fill up the entire meatus. There may be slight conduction deafness also due to mechanical obstruction of the external auditory canal. The local area may be hyperemic and sometimes bleeding may be observed. In immunocompromised patients especially diabetics, Aspergillus may invade locally to adjacent anatomical sites like mastoid bone or even brain.

Aspergillus may cause invasive external otitis (necrotizing or malignant otitis externa) with local spread to bone and cartilage, which is a severe and potentially life-threatening disease (Carfrae et al, 2008). This may be associated with underlying immunocompromised situation, diabetes mellitus or patient receiving haemodialysis entailing high mortality. Invasive otitis externa is more frequently caused by A. fumigatus than A. niger (Reiss et al, 1991; Strauss et al, 1991; Yates et al, 1997; Munoz et al, 1998; Chen et al, 1999; Rutt et al, 2008). In addition, invasive Aspergillus tympanomastoiditis may be encountered in immunocompetent patients as well (Bryce et al, 1997). Recently efficacy of antifungal therapy with voriconazole 200 mg twice a day in invasive otitis externa caused by Aspergillus has been reviewed (Parize et al, 2008).

Differential Diagnosis
Otomycosis needs to be differentiated from similarly looking clinical entities such as bacterial otitis externa, seborrheic dermatitis, impetigo, furunculosis and contact dermatitis.

Laboratory Diagnosis
The clinical diagnosis of otomycosis should be supplemented by microscopy and culture of debris material taken out from the external auditory canal or mastoid area like cholesteatoma. The presence of fungal structures is seen in potassium hydroxide (KOH), calcofluor white or blankophor wet mounts. The microscopic examination shows discrete clumps of hyphae with conidiophores. In otitis externa caused by A. niger, septate hyphae, sporulating vesicles and abundant black spores are seen. Immunofluorescence microscopy, using fungal-specific monoclonal antibodies, has been performed as a rapid, accurate and sensitive diagnostic technique (Gurr et al, 1997).

If tympanic membrane perforation is observed, A. fumigatus cultured, local invasion is clinically apparent or the patient is immunocompromised, invasive otitis externa should be suspected. Radiological techniques like CT scan or MRI are done to delineate any involvement of the adjoining anatomical sites. If infection appears to involve the middle ear and mastoid, biopsy should be taken for direct demonstration of invasive fungal infection as well as fungal culture.

Treatment
Careful drying and cleaning of external auditory canal is the first step in treatment, which is done preferably by suction evacuation (Patow, 1995). Syringing of external auditory canal should be avoided as it may sometimes lead to flare up of the infection to deeper anatomical sites, particularly when the tympanic membrane is perforated and is not visible due to impacted debris material overlying it. If the facilities of suction evacuation are not available, syringing should be done under all aseptic conditions with normal saline mixed with antifungal powder. The ear should be mopped up absolutely dry following syringing as moisture support continued growth of fungi. Although slightly painful, methylated spirit may be used to dry mop the ear.

Topical Therapy
Antifungal treatment of otomycosis depends upon the nature of the disease, especially whether it is uncomplicated or complicated where breech in the surface of the external auditory canal. The topical therapy with antifungal or other antimicrobial agents is also necessary. Effective choices include amphotericin B (3%), flucytosine (10%), econazole cream (1%), clotrimazole cream, powder or solution (1%), thiomersal (Merthiolate) or Cresyl acetate solution. Salicylic acid, griseofulvin and ketoconazole are less effective. Econazole (1%) solution is very effective in vivo in the treatment of otomycosis within 1-3 weeks (Bassiouny et al, 1986). This may be valuable in cases of mixed otitis externa owing to high broad-spectrum antifungal activity as the treatment of choice in otomycosis and can be used safely as otic drops. If the tympanic membrane is perforated, tolnaftate 1% solution (Tinactin) should be used in order to prevent ototoxicity.

The other mode of treatment is by applying antifungal ointment to the external auditory canal. The only drawback of powder and ointment is that the patient himself can not apply it properly and needs to visit the otologist. The simplest method is after the initial small cotton/gauge nick in the external canal and keeps on pouring antifungal drops over it at regular interval. An alternative is simply asking the patient to put 4-6 drops and he should be lying in lateral position with affected ear upward for 10-15 minutes. The patient is examined after a gap of one week for follow up.

Mercurochrome, a water-soluble organic mercurial compound, is commonly used as an antibacterial agent and also known to have antifungal properties on topical application. It is often used as 1-2% solution (Chander et al, 1996) and has been specifically used in cases with humid environments with a reported efficacy range between 96% and 100% (Mgbor et al, 2001; Mishra et al, 2004). However, it is no longer approved by FDA due the fact that it contains mercury.

In rural areas of some of the developing countries, people are traditionally putting various types of oils in their external auditory canal. However, many studies have now shown that these oils are antifungal in nature, endorsing the therapeutic relevance of such tradition. Keratolytic agents with nonspecific activity such as boric acid are widely used. Administration of 4% boric acid solution in alcohol and frequent suction cleaning of the ear canal might be a cost-effective treatment for otomycosis since 77% of the patients were treated effectively in this way (del Palacio et al, 2002). A randomized controlled trial of the treatment of otitis externa found 1% silver nitrate gel to be useful in 92% of patients (van Hasselt et al, 2004).

Antifungal drops, given three or four times daily for five to seven days, are usually adequate to complete treatment. Because the infection can persist asymptomatically, the patient should be re-evaluated at the end of the course of treatment. At this time any further cleansing can be performed as needed. Aspergillus infections may be resistant to clotrimazole and may require the use of oral itraconazole.

Systemic antifungal therapy
Systemic antifungal therapy is only required if patients fail topical therapy or have invasive external otitis. Itraconazole can be used for superficial otitis externa, but any invasion, including perforation of the tympanic membrane should be treated with voriconazole. Tympanoplasty might be needed if the perforations do not heal spontaneously (Wang et al, 2005).

Itraconazole resistance in A. fumigatus and A. niger are described in isolates causing otomycosis (Kaya et al, 2007) as well as more widely (Snelders et al, 2008). It is not known if such isolates are resistant to econazole but this is likely. Some may be resistant to voriconazole and posaconazole.

Professor Jagdish Chander
Department of Microbiology, Government Medical College Hospital, 
Sector 32, Chandigarh, India - 160030. 
[email protected]

February, 2009

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