Table 1 – (Appendix – to be inserted here)
Discussion
Otitis externa is a common otological problem encountered regularly by
clinicians in primary and secondary care. The data from more than 40
emergency departments in 2007, revealed 2.4 million visits for acute
otitis externa (8.1 visits per 1000 population), affecting nearly 1 in
123 across the population of the United States. The lifetime incidence
has been reported to be up to 10%. (11)
Studies from other countries also support this observation. A survey
performed in a general hospital in Spain over 12 months, reported otitis
externa to be accounted for 14.8% of referrals to otolaryngologist from
emergencies, becoming the second most common aetiology referred to
otolaryngologists following epistaxis (16.8%). (14)
The direct costs of managing otitis externa have been estimated at
around half a billion dollars annually in the United States. This figure
only covers the costs of hospital visits and treatment prescriptions.
(15) Indirect costs are likely to be substantial due to the disabling
effect of the disease. In one study published in the Netherlands, the
condition found to cause a discontinuation of daily activity and bed
rest for 36% (35/98) of patients, for a median of four days, and 21%
(21/98) required bed rest and time off work for a median of 3 days. (16)
The magnitude of resistant chronic cases was demonstrated well in a
national epidemiological survey published in 2001, which investigated
the prevalence and treatment regimen used in primary care to treat
otitis externa in the UK. The data derived from the General Practice
Research Database (GPRD) which analysed GP visits related to 40,661
episodes of otitis externa in more than thirty thousand patients,
revealed 21% of patients suffered from more than one episode and a
further 7% visited their GP three or more times for persistence and/or
recurrence of otitis externa over a one-year period. In addition, 3% of
patients had to be referred to ENT specialists for further treatment and
expert opinion. (9) It is likely that resolving
chronic otitis externa will decrease the episodes of acute otitis
externa a patient sustains.
Many otolaryngology departments across the National Health Service (NHS)
in the UK have now established ‘casualty’ or ‘emergency’ clinics which
are commonly led by junior trainees and receives referrals from General
Practices and Emergency Departments (ED). The high prevalence of otitis
externa in these clinics have been demonstrated previously. Data from a
tertiary hospital in the UK, indicates that between 16-20% of new
referrals and almost 30% of daily follow-ups are related to otitis
externa.(17)
Further analysis of findings demonstrates that otitis externa is the
most common condition seen more than twice in a single clinical episode.
The data obtained from ENT emergency clinic in St. George’s Hospital in
London shows that 80% of such repeated visits are related to cases of
otitis externa not responding to treatments offered in the initial
visit, required further follow up and input by senior clinicians. (18)
Similar challenging cases of otitis externa has been encountered in our
centre, where they have been referred to the senior author of this
paper, by which time most conventional treatments have been exhausted.
There is no guideline in the United Kingdom for the management of
chronic otitis extern. Although there have been few randomized
controlled trial involving chronic cases along with acute otitis
externa, no single recommendations can be derived for the treatment of
chronic otitis externa as a separate clinical disorder.(1)
Other than the conventional combination of topical steroids, topical and
oral antibiotics, two novel approaches have been taken recently for
treatment of chronic otitis externa, including use of Tacrolimus and
Fluocinolone acetonide solution.
Tacrolimus ointment is a nonsteroidal topical immunomodulator that was
formulated specifically for the treatment of atopic dermatitis.(19) The
ointment effectiveness has been evaluated in a German prospective study,
for management of 33 patients with chronic otitis externa. The
medication was applied topically for a period of 6 to 9 days and the
results showed 13 out of 33 patients (39%) with complete healing
(follow up 10-22 months). Total of 15 cases were recorded to have
relapse within the same period. (20)
A randomized controlled trial (RCT) looked into the safety and efficacy
of fluocinolone acetonide 0.025% solution (a low-to-medium
corticosteroid) in treatment of otic eczema, which is often a chronic
and relapsing condition difficult to manage.
This RCT measured changes in symptoms including itching and otoscopic
signs after administration of fluocinolone acetonide 0.025% solution
twice daily for 7 days and compared it with a placebo-treated group.
Results indicated that patients treated fluocinolone acetonide solutions
(n= 58), compared with the placebo-treated group (n= 63), had
significantly higher reduction in itching (P < 0.001) and
improvement in otoscopic signs (P < 0.001). (21)
We have investigated the option of using Flixonase®topically in 25 resistant cases. As presented in the section above, all
cases who returned to follow up were classified as being cured and
symptoms free. When applied topically, fluticasone propionate, a potent
corticosteroid, relieves pruritic and inflammatory symptoms through
binding and activation of glucocorticoid receptors. This trigger a
cascade of reactions involved in the synthesis of prostaglandins. The
results include alteration of protein synthesis, decreased fibroblast
proliferation, reduction in the release of leukocyte acid, reduced
capillary membrane permeability, less collagen deposition, inhibition of
histamine and kinin release and prevention of macrophage accumulation.
(22,23)
It should be noted that more than 70% of our patients used treatment
modalities which contained corticosteroids, with
Sofradex® and Gentisone HC ear drops being the most
common ones. A comparison between the steroid concentration of all three
drops, shows that daily dosage of fluticasone propionate contains
significantly higher concentration of corticosteroids, compare to the
other two ear drops. Sofradex® ear drop (0.5% w/v of
Framycetin, Sulphate 0.005% w/v of Gramicidin and 0.050% w/v of
Dexamethasone) contains 50 micrograms of corticosteroid per 100 ml; when
applied topically, it will deliver 0.3 micrograms of corticosteroid to
the external ear canal. * Gentisone HC ear drops
(Gentamicin 0.3% w/v and Hydrocortisone acetate 1% w/v Ear Drops)
contains 1000 micrograms of corticosteroid per 100 ml; which is
equivalent to 8 micrograms of steroid per day. **Given that 200micrograms/day fluticasone propionate was prescribed, the
significant difference in the amount of highly potent corticosteroid
delivered to the external ear canal could explain the successful
response observed in cure rate of resistant cases with a course of
Flixonase® alone.
* Maximum dosage of Sofradex® is 3 drops, QDS,
assuming each drop containing 0.05 ml, the total daily volume of
Sofradex® delivered topically equals 0.6 ml
** Maximum dosage of Gentisone HC is 4 drops QDS, assuming each drop
containing 0.05 ml, the total daily volume of Gentisone HC delivered
topically equals 0.8 ml
A study done to compare systemic exposure of intranasal steroids
confirmed that delivery of therapeutic dose of 2400 micrograms of
fluticasone propionate daily will result in very low systemic
bioavailability, estimated to be 0.06% (24). Given the fact that
Flixonase was prescribed topically to the skin, not mucosa, the systemic
bioavailability is likely to be lower than the figure cited above
(< 0.06%). Hence, it can be concluded that fluticasone
propionate is likely to produce very small systemic exposures to
steroids, and have a low potential for systemic side effects when
administered topically to ears at the recommended doses.
There are however some limitations to our work. The first is the
variable length of treatment for each patient. This can be attributed to
more difficult cases, or to potentially concurrent skin conditions such
as psoriasis or eczema which can attribute to recurrent disease. The
second limitation is the restricted number of patients and those lost to
follow up. Although, a small cohort size this treatment modality does
show promise within a domain notoriously difficult to treat.