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\begin{document}

\title{A review of the management of fungal otitis externa with necrosis of the
tympanic membrane: An additional of 2 cases to the literature.}



\author[1]{Yasmin Abbas}%
\author[2]{Nitesh Patel}%
\affil[1]{Northwick Park Hospital}%
\affil[2]{Whipps cross university hospital}%


\vspace{-1em}



  
  \date{May 27, 2024}


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\selectlanguage{english}
\begin{abstract}
* A high index of suspicion is needed when otitis externa not improving
and there are symptoms of significant pruritis. * Signs of fungal
debris, either obvious spores or black particles in debris should alert
one to take a microbiology swab for fungal culture, which may yield
Candida or Aspergillus species. * Treat patients with regular and prompt
microsuctioning and application of topical antifungals for up to a
month: Aspergillus can be particularly aggressive and lead to tympanic
membrane erosions, ulceration and perforation. * Flumetasone/Clioquinol
drops are effective in Aspergillus fungal otitis externa * Consider
surgical repair if tympanic membrane not healed with medical treatment.%
\end{abstract}%



\sloppy


\textbf{Key points}

A high index of suspicion is needed when otitis externa not improving
and there are symptoms of significant pruritis.

Signs of fungal debris, either obvious spores or black particles in
debris should alert one to take a microbiology swab for fungal culture,
which may yield Candida or Aspergillus species.

Treat patients with regular and prompt microsuctioning and application
of topical antifungals for up to a month: Aspergillus can be
particularly aggressive and lead to tympanic membrane erosions,
ulceration and perforation.

Flumetasone/Clioquinol drops are effective in Aspergillus fungal otitis
externa

Consider surgical repair if tympanic membrane not healed with medical
treatment.

\textbf{Background}

Otitis externa due to fungal pathogens more commonly presents in
diabetic and immunocompromised patients. The symptoms are similar to
those with other causes of otitis externa; pruritis, ottorhoea, otalgia
and reduced hearing from oedema and/or accumulation of
debris\textsuperscript{1-4}. Fungal pathogens are the cause of 10\% of
otitis externa and lead to a loss of the protective lipid/acid balance
of ear. The predominant causative pathogens are Candida and Aspergillus
species\textsuperscript{2,3,5} colonising the squamous epithelium of the
external auditory canal. The mainstay of treatment is a combination of
microsuctioning, debridement and topical antifungal
treatment.\textsuperscript{3,6}

This paper aims to summarise the management of tympanic membrane
perforations secondary to fungal otitis externa, an infrequently
reported consequence of suboptimal management of this condition.

\textbf{Methodology}

A literature review identified 15 papers, which were filtered down to 6
relevant papers with case series of tympanic membrane perforations
secondary to fungal otitis externa in humans in the English literature
after the following search was carried out (((perforation) AND (tympanic
membrane)) AND ((otomycosis) AND fungal otitis externa) in pubmed on
30/3/21

These were reviewed and the findings presented together with our two
cases which provide photodocumentation to further add to the literature.
The SCARE criteria was used to report these cases

\textbf{Ethical Considerations}

This study complies with the declaration of Helsinki.



\textbf{Results}

\emph{Case 1:} A 54 year old female presented with a 2 month history of
bilateral ear irritation associated with hypoacusis, tinnitus and
otalgia. She had no previous ear symptoms. Previous treatment included
betnesol drops for 1 week and otomise ear spray for 1 week. Microscopic
examination of the ear canal revealed a perforation of the left tympanic
membrane and visible fungal spores. Microbiological swab was sent, which
grew Aspergillus niger species. A one week course of Flumetasone
Pivalate 0.02\% / Clioquinol 1.0\% ear drops was given. After one month,
there was some improvement of the clinical picture with respect to the
otalgia and some closure of the tympanic membrane perforation which was
now dry but not complete closure, hence a tympanoplasty was performed
with resultant normal hearing on the audiogram. (Figure 1)

\emph{Case 2:} 39 year old female presented with left otalgia,
hypoacusis and ottorhoea. A one week course of sofradex ear drops were
unhelpful. Microscopic examination revealed debris which was
microsuctioned to reveal multiple tympanic membrane perforations. A
microbiological swab grew Aspergillus niger species. A one week course
of Flumetasone Pivalate 0.02\% / Clioquinol 1.0\% ear drops resulted in
full resolution of symptoms and closure of the tympanic membrane
perforations. (Figure 2) The post-treatment audiogram was normal.

\emph{}

\textbf{Discussion}

\emph{Synopsis of key findings:}

Patients with fungal otitis externa typically present with swelling and
erythema of the external auditory canal and report otalgia, otorrhoea,
itching and hypoacusis.\textsuperscript{1,2,5} Symptoms of itching and
otorrhoea were more common in immunocompetent patients whereas otalgia,
blocked sensation, decreased hearing and tinnitus were noted more in
immunocompromised patients.\textsuperscript{4,6}

Examination findings include oedema and serous transudate of external
canal skin, erythema and perforation of a thickened tympanic membrane,
as well as serous discharge from the middle ear into the external
auditory canal.\textsuperscript{1}

There is a consensus in the literature that the responsible pathogens
were Candida and Aspergillus spp.,\textsuperscript{2,5} with the former
being more common in immunocompromised patients.\textsuperscript{6}

The prevalence of otomycosis is reported to be between
9\%\textsuperscript{4} -- 30.4\%.\textsuperscript{5} The identified risk
factors include humid climates, chronic otitis, lack of
cerumen\textsuperscript{2} as well as extensive and unnecessary use of
both topical and systemic antibiotics.\textsuperscript{2} There was also
a higher incidence noted in male patients.\textsuperscript{4,6} Ho et
al. found an increased risk of otomycosis with previous otological
procedures, as well as the presence of a mastoid
cavity.\textsuperscript{4}

The study by Jackman et al was key in our understanding of the
contribution of topical antibiotic drops such as Ofloxacin to the
development of otomycosis. The mechanisms are two fold: it's action as a
bactericidal allowing fungal proliferation due to the lack of competing
bacterial growth as well as it's neutral pH allowing an optimal
environment for fungal growth. The proposed pathophysiology was that
perforations form after sub-epithelial abscess develops on the tympanic
membrane. Fungus causes thrombosis in adjacent blood vessels, which
produces avascular necrosis of the underlying tympanic membrane
resulting in a perforation.\textsuperscript{7}

\emph{Strengths of this study}

Within the literature, there are 169 reported cases of tympanic membrane
perforations secondary to fungal pathogens, we add 2 more cases with the
benefit of photodocumentation, summarise the management in the
literature and suggest a management algorithm for these cases.

\emph{Comparison with other studies}

The largest case series from a single institution is that by Lou et al.
in which a prospective case series of 74 patients with unilateral
chronic tympanic membrane perforations due to otomycosis were treated
with ketoconazole cream and this was reapplied weekly until no
otomycosis were visible for 2 consecutive weeks and then scheduled for
cartilage myringopalsty. They reported a 83.8\% graft take at 6 months
with 6.8\% developing post-operative otorhhoea and reperforations and
9.5\% have recurrent otomycosis. \textsuperscript{8}

Abou-Halawa et al, performed a prospective study within an ambulatory
setting of 40 patients with otomycosis and tympanic membrane
perforations. This demonstrated the efficacy of self-medicated
clotrimazole using Q-tips versus physician inserted wicks coated with
clotrimazole. The follow up of 3 months demonstrated recurrence of
otomycosis in 5 patients in the ear wick group compared to zero in the
self-medicated group. Three patients in Q-tip group and one in ear wick
group had closure of their tympanic membrane
perforation.\textsuperscript{9}

Hurst produced a case series of 22 patients, who typically presented
with a discrete white and opaque area on the tympanic membrane which
after a week disintegrates to leave a perforation. Treatment was that of
microsuction of epithelial and fungal debris from the ear canal and use
of gauze wick coated in clotrimazole, hydrocortisone, framycetin,
gramicidin every 2 days until resolution. Resolution of the otitis
externa allows the perforation to heal with a normal tympanic membrane
within a month and had no residual hearing loss in the majority (86.3\%)
of cases. Three of this cohort required intervention: 2 myringoplasty
and 1 cauterisation to fully close. \textsuperscript{10}

Rutt reported a case of an immunocompromised patient with chronic left
otitis media and multiple recurrent tympanic membrane perforations. This
was initially treated with antibiotics and antifungal drops, then had a
transcanal tympanoplasty and resection of middle ear cholesteatoma. The
graft failed but the patient respond well to oral fluconazole and
clotrimazole drops with no further recurrences. The paper concluded that
treatment should be vigorous, especially in immunocompromised patients
to prevent complications such as hearing loss and invasive temporal bone
infections.\textsuperscript{3}

A prospective clinical study by Viswanatha compared 50 cases of
otomycosis in immunocompetent versus 50 cases of immunocompromised
patients. The 21-30 age group had the highest incidence in
immunocompetent patients, whereas 41-50 year olds were more frequently
affected in the immunocompromised group. Three percent of patients had
tympanic membrane perforation, all of which were in the
immunocompromised group. All patients were initially treated with
clotrimazole ear drop for 3 weeks, 4 in immunocompromised group didn't
respond and so were treated successfully with fluconazole drops.
Patients were advised regarding ear water precautions for 3
weeks.\textsuperscript{6}

A case series of 11 patients; 8 men and 3 women aged 18-70 (mean 46)

presenting with chronic, treatment-refractory otitis externa found that
63\% had no prior ear complaints. Treatment was debridement and topical
antifungal application (boric acid, nystatin, oral fluconazole or
Ciprofloxacin, chloramphenicol, amphotericin and hydrocortisone). Full
resolution and closure of the tympanic membrane was found in 8 of 11
cases, 2 had tympanoplasty procedures and 1 had a fat graft
myringoplasty. Song concluded that most cases of tympanic membrane
perforations secondary to fungus resolve with medical
treatment.\textsuperscript{1}

Ho presents a retrospective review of 132 patients with otomycosis, 18
of which had a perforation and only 1 required tympanoplasty. Topical
ketoconazole for a period of up to 3 weeks was found to have higher
resolution and lower recurrence rate than other
treatments.\textsuperscript{4}

A retrospective study over 6 years, identified 103 patients with
mycological diseases of the ear canal based on microscopic examination
and culture.\textsuperscript{2}

Kurnatowski treated 381 cases of otitis externa with daily aural toilet
and instillation of fluconozole three times a day and led to a 89\% cure
with no response in 5.77\% of cases.\textsuperscript{5}

\emph{Clinical applicability of the study}

A review of the literature shows a clear agreed trend on how to manage
patients presenting with fungal otitis externa. We have summarised the
trends in a management algorithm (Figure 3).

\textbf{Conclusion}

Fungal otitis externa is a diagnosis to be aware of in patients that are
not improving with usual treatment for bacterial otitis externa. If left
untreated, this can result in perforations of the tympanic membrane
requiring a strict regimen of topical medication and regular
microsuctioning for up to 1 month. A high index of suspicion is required
to prevent surgical intervention.

\textbf{List of figures}

Figure 1: Clinical progression of case 1 following treatment.

Figure 2: Demonstration of tympanic membrane perforations secondary to
fungal otitis externa

Figure 3: A management algorithm for fungal otitis externa



\textbf{References}

\begin{enumerate}
\tightlist
\item
  Song JE, Haberkamp TJ, Patel R, Redleaf MI. Fungal otitis externa as a
  cause of tympanic membrane perforation: a case series. Ear Nose Throat
  J. 2014 Aug;93(8):332-6.
\item
  da Silva Pontes ZB, Silva AD, de Oliveira Lima E, de Holanda Guerra M,
  Oliveira NM, Carvalho MD, Guerra FS. Otomycosis: a retrospective
  study. Brazilian Journal of otorhinolaryngology. 2009 May
  1;75(3):367-70.
\item
  Rutt AL, Sataloff RT. Aspergillus otomycosis in an immunocompromised
  patient. Ear Nose Throat J. 2008 Nov;87(11):622-3.
\item
  Ho T, Vrabec JT, Yoo D, Coker NJ. Otomycosis: clinical features and
  treatment implications. Otolaryngology---Head and Neck Surgery. 2006
  Nov;135(5):787-91
\item
  Kurnatowski P, Filipiak A. Otomycosis: prevalence, clinical symptoms,
  therapeutic procedure. Mycoses. 2001 Dec 1;44(11-12):472-9.
\item
  Viswanatha B, Sumatha D, Vijayashree MS. Otomycosis in immunocompetent
  and immunocompromised patients: comparative study and literature
  review. Ear Nose Throat J. 2012 Mar;91(3):114-21. Review.
\item
  Jackman A, Ward R, April M, Bent J. Topical antibiotic induced
  otomycosis. International journal of pediatric otorhinolaryngology.
  2005 Jun 1;69(6):857-60.
\item
  Lou Z. The evaluation of endoscopic cartilage myringoplasty to repair
  perforations with otomycosis. American journal of otolaryngology. 2020
  Jul 1;41(4):102493.
\item
  Abou-Halawa AS, Khan MA, Alrobaee AA, Alzolibani AA, Alshobaili HA.
  Otomycosis with Perforated Tympanic Membrane: Self medication with
  Topical Antifungal Solution versus Medicated Ear Wick. Int J Health
  Sci (Qassim). 2012 Jan;6(1):73-7.
\item
  Hurst WB. Outcome of 22 cases of perforated tympanic membrane caused
  by otomycosis. J Laryngol Otol. 2001 Nov;115(11):879-80.
\end{enumerate}

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