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\begin{document}

\title{Sensory neural hearing loss in Behcet's disease successfully controlled
with infliximab, case report and review of literature.}



\author[1]{Mohanad Faisal}%
\author[1]{Haider Barjas}%
\author[1]{Wisam Alwassiti}%
\author[1]{Walid omer}%
\author[1]{Nabeel Abdulla}%
\affil[1]{Hamad Medical Corporation}%


\vspace{-1em}



  
  \date{June 02, 2024}


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\selectlanguage{english}
\begin{abstract}
Behcet's disease is a systemic autoimmune disorder occasionally
associated with otological manifestations, including sensorineural
hearing loss. We are reporting a case of Behcet's disease, which was
complicated by sensorineural hearing loss and managed successfully with
anti-TNF agent Infliximab.%
\end{abstract}%



\sloppy


\textbf{Sensory neural hearing loss in Behcet's disease successfully
controlled with infliximab, case report and review of literature.}

Mohanad Faisal*, Haidar Barjas, Wisam Alwassiti, Walid Omer, Nabeel
Abdulla.

Hamad medical corporation, Doha, Qatar.

*Corresponding author: mmfobaidy@gmail.com

\textbf{Abstract:}

Behcet's disease is a systemic autoimmune disorder occasionally
associated with otological manifestations, including sensorineural
hearing loss. We are reporting a case of Behcet's disease, which was
complicated by sensorineural hearing loss and managed successfully with
anti-TNF agent Infliximab.

\textbf{Key clinical massage:}

To provide review about the interesting association between Bechet's
disease and sensory-neural hearing loss and the possibility of managing
this manifestation of Behcet's disease with anti TNF agent like
infliximab.

\textbf{Introduction:}

Behcet's disease is a vasculitis affecting small to medium and even
large vessels (arteries and veins). It is primarily characterized by
recurrent oral ulcers, genital ulcers, skin and ophthalmological
manifestations such as uveitis. It is most prevalent in the ancient silk
road from Eastern Asia to the Mediterranean. It is common in Turkey,
with a prevalence of 350/100,000 population. Cases have been reported in
Northern America and Europe as well. This syndrome can affect males and
females in most regions, typically between 20-40 years of age at the
onset of the disease. Carriers of HLA-B5 and HLA-B51 are more prone to
develop Behcet's disease than non-carriers. It is thought that an
infectious or environmental antigen triggering an autoimmune response in
genetically predisposed individuals is behind its pathogenesis.
Diagnostic criteria for Behcet's disease require the presence of oral
ulcers and any of the following: genital ulcers, typical eye lesions,
typical skin lesions, or a positive pathergy test {[}1{]}. Treatment of
Behcet's disease depends on its manifestation, whether oro-genital
ulcers, ocular disease, vasculitis, arthritis, gastrointestinal or
neurological manifestations. Recurrent oro-genital ulcers are usually
treated with colchicine alone. At the same time, significant
manifestations like posterior uveitis, vasculitis, and gastrointestinal
disease usually require high-dose glucocorticoid along with another
immunosuppressive agent. {[}2{]}.

Here, we present a 37-year-old Middle Eastern male patient with Behcet's
disease with recurrent episodes of bilateral sensorineural hearing loss
that responded well to oral prednisolone, Infliximab, and Azathioprine.

\textbf{Case Presentation:}

We present our case, which is a 37-year-old male middle eastern with a
past medical history of Haemophilia A. He presented to our outpatient
ophthalmology clinic with a right eye sudden decrease in vision for four
days. On evaluation of the eye, he had features of unilateral
pan-uveitis with para-macular retinitis, mild vitritis, peripheral
punctuate retinal hemorrhage, and macular exudative retinal detachment,
findings highly suggestive of Beh\selectlanguage{ngerman}çet's disease. He was started on a
tapering dose of oral prednisolone and referred urgently to the
Rheumatology clinic. Upon enquiring, he mentioned a history of recurrent
painful oral and genital ulcers for several years for which he did not
seek medical attention before. On review of systems, he had no history
of joint pain or swelling, no history of skin rash, respiratory or
gastrointestinal symptoms, and no history of deep vein thrombosis.

On examination, no oral ulcers or scars were present, but he had one
papule on the scrotum. Review of other systems were unremarkable. Blood
tests (table.1) at this point were unremarkable, including autoimmune
screening apart from slightly elevated C-reactive protein (CRP, 17
mg/dl). HLA typing for HLA-B51 was negative. Pathergy test was negative.
A clinical diagnosis of Behçet's disease was made based on history of
recurrent painful oral ulcers, genital ulcers and panuveitis. Hence,
Immunosuppressive therapy was started with prednisolone, azathioprine
and infliximab.

After a few weeks of treatment, his vision improved with a resolution of
signs of uveitis. He was maintained on azathioprine and infliximab, with
the latter stopped after 15 months.

The patient was referred after seven months to an audiology clinic for
evaluation of tinnitus and hearing loss. Symptoms of hearing loss had
started in left ear almost at the time of panuveitis but it stabilized
after starting immunosuppression and later involved the right ear, few
months after stopping Infliximab. Physical examination of the ears were
normal, with intact tympanic membrane bilaterally. A pure tone audiogram
showed bilateral sensorineural hearing loss more on high frequencies
(Figure 1). Magnetic resonance imaging (MRI) of the head and internal
auditory meatus was done and were normal (Figure 2). All vestibular
tests including video-nystagmography, oculomotors and post headshake
test, computerized dynamic posturography, caloric testing, vestibular
evoked myogenic potential and video head impulse test were unremarkable.
Based on the previous diagnosis of Behçet's disease, the sensorineural
hearing loss was attributed to cochlear involvement by autoimmune inner
ear disease related to Behçet's disease. The patient was kept under
close follow-up by Rheumatology, Ophthalmology, and Audiology. He was
started on oral steroid prednisolone 70 mg per day for one month in
addition to 4 doses of intratympanic steroid injections, which partially
relieved symptoms. However, he continued to have repeated hearing loss
episodes whenever steroid doses were tapered. Infliximab was resumed as
a steroid-sparing agent with a dose of 5mg/kg every six weeks, along
with azathioprine 100 mg per day and it helped to successfully taper and
stop steroid. The patient was followed for the next two years, and his
symptoms were controlled with stable audiogram levels.

\textbf{Discussion}

Behcet's disease is a type of vasculitis that affects arteries and veins
of any size. Its presentation commonly involves the mucus membranes,
skin, and vasculature. It has an autoimmune etiology after exposure to
specific environmental or infectious agents in genetically prone people.
The otologic manifestations of Behcet's disease include anything from
tinnitus to sensorineural deafness {[}3{]}.

Our case was a known Behcet's disease gentleman who presented with
recurrent episodes of sensorineural hearing loss, which was attributed
to an autoimmune pathology because of his Behcet's disease.

Literature review using Pubmed search has shown multiple case series and
case reports of sensorineural deafness as a manifestation in patients
with Behcet's disease. A retrospective review of 33 patients with
Behcet's disease in tertiary hospital in Spain showed 5 (15\%) of total
patients had audiovestibular symptoms (including sensorineural hearing
loss, vertigo, and bilateral vestibular dysfunction) {[}3{]}. Another
study which included 63 subjects with Behcet's disease and 63 sex and
age-matched healthy subjects as a control group showed that 35 patients
(55\%) had hearing loss equal or more than 30 Decibell (DB) and 24 of
the 35 patients (68\% of the patients with hearing loss) showed hearing
loss at higher frequencies of (6-8 kHz) {[}4{]}. In another study which
recruited 62 Behcet's disease patients and compared with 62 healthy
subjects, around 32\% (20 of the 62 Behcet's patients) had evidence of
sensorineural deafness (at 25 DB in at least two frequencies) by pure
tone audiogram, all of the 20 patients with hearing loss had cochlear
involvement evidenced by the recruitment investigation tests and
auditory brain stem response. 15/20 patients with hearing loss had
HLA-B51 antigen-positive {[}5{]}.

In a prospective placebo-controlled study that included 29 patients with
Behcet's disease and 28 normal subjects, pure tone audiometry (PTA) and
transient evoked otoacoustic emission (TEOAE) were determined, and it
was found that 10 out of the 29 patients with Behcet's disease had
sensorineural hearing loss (34.5\%) at 1,2,3,4, and 8 kHz (p\textless{}
0.498) and this was statistically significant compared to the control
group. The difference in TEOAE levels that revealed sound to noise ratio
between the two groups was statistically not significant at 1, 1.5, 2,
and 3 but was significant at 4 kHz (p\textless{}0.02), and the
difference was reproducible (p\textless{}0\textgreater{}03) {[}6{]}

In a review, 24 Behcet's disease patients with 24 age and sex-matched
healthy subjects as control groups were studied to investigate hearing
loss in Behcet's disease. It showed that 15 of the 24 subjects with
Behcet's disease had sensorineural deafness {[}7{]}.

In another study of 35 subjects with Behcet's disease compared with 35
healthy subjects as a control group and were followed up for a year, 28
patients with Behcet's disease (80\%) showed some degree of hearing loss
{[}8{]}.

Some case reports about the association between Behcet's disease and
sensorineural hearing loss were also found in the literature {[}9{]}
{[}10{]} {[}11{]}.

A possible pathophysiological explanation for the sensorineural hearing
loss in Behcet's disease includes autoimmune inflammation of the common
cochlear artery affecting primarily the cochlea's outer hair cells
resulting in decreased sensitivity and impaired sound evoked neural
activity. {[}8{]}

Anti- TNF is usually used in refractory Behcets disease manifestations,
mainly sight-threatening disease with frequent relapse of uveitis in
addition to other refractory manifestations {[}12{]}. But its use in
sensorineural hearing loss is less well established.

Possible treatment options for the sensorineural loss in Behcet's
disease include high dose systemic steroids initially followed by
steroid sparing agents, intratympanic steroid injections and hyperbaric
O2 therapy {[}9{]} {[}10{]}. Initial management for our patient was with
oral prednisolone 70 mg and intratympanic steroid injection, which
successfully controlled his symptoms with partial improvement and
decreased the acute attacks rate. However, the symptoms recurred once
the steroid dosage was reduced. So, we started him on infliximab and
later azathioprine was added, both successfully helped to control his
symptoms and discontinue steroid.

\textbf{Conclusion:}

Clinicians should keep in mind that Behcet's disease is not uncommonly
associated with sensorineural hearing loss, and that anti-TNF and
steroid-sparing agents could help control the disease if other
modalities fail. Further studies are needed to prove the efficacy of
anti-TNF in this setting.

\textbf{References}

\textbf{1-} Criteria for diagnosis of Behçet's disease. International
Study Group for Behçet's Disease. (1990). \emph{Lancet (London,
England)} , \emph{335} (8697), 1078--1080.

\textbf{2-} Hatemi, G., Silman, A., Bang, D., Bodaghi, B., Chamberlain,
A. M., Gul, A., Houman, M. H., Kotter, I., Olivieri, I., Salvarani, C.,
Sfikakis, P. P., Siva, A., Stanford, M. R., Stubiger, N., Yurdakul, S.,
\& Yazici, H. (2008). EULAR recommendations for the management of Behcet
disease. \emph{Annals of the Rheumatic Diseases} , \emph{67} (12),
1656--1662. https://doi.org/10.1136/ard.2007.080432

\textbf{3-} Morales-Angulo, C., Vergara Pastrana, S., Obeso-Agüera, S.,
Acle, L., \& González-Gay, M. Á. (2014). Manifestaciones
otorrinolaringológicas en pacientes con enfermedad de Behçet. \emph{Acta
Otorrinolaringológica Española} , \emph{65} (1), 15--21.
https://doi.org/10.1016/j.otorri.2013.06.007

\textbf{4-} AK, E., Harputluoglu, U., Oghan, F., \& Baykal, B. (2004).
Behçet's disease and hearing loss. \emph{Auris Nasus Larynx} ,\emph{31}
(1), 29--33. https://doi.org/10.1016/j.anl.2003.07.006

\textbf{5-} Kulahli, I., Balci, K., Koseoglu, E., Yuce, I., Cagli, S.,
\& Senturk, M. (2005). Audio-vestibular disturbances in Behcet's
patients: report of 62 cases. \emph{Hearing Research} , \emph{203}
(1--2), 28--31. https://doi.org/10.1016/j.heares.2004.11.020

\textbf{6-} Kemal, O., Anadolu, Y., Boyvat, A., \& Tatara\selectlanguage{polish}ğ\selectlanguage{english}asi, A.
(2013). Beh\selectlanguage{ngerman}çet Disease as a Cause of Hearing Loss: A Prospective,
Placebo-Controlled Study of 29 Patients. \emph{Ear, Nose \& Throat
Journal} , \emph{92} (3), 112--120.
https://doi.org/10.1177/014556131309200309

\textbf{7-} Aslan, S., Serarslan, G., Savas, N., Teksoz, E., \& Dagli,
S. (2010). Hearing loss in patients with Behçet's disease: an
audiological and transient evoked otoacoustic emission study. \emph{The
Journal of Laryngology \& Otology} , \emph{124} (1), 10--15.
https://doi.org/10.1017/S0022215109991083

\textbf{8-} Elidan, J., Cohen, E., Levi, H., \& BenEzra, D. (1991).
Effect of Cyclosporine a on the Hearing Loss in Behçet's
Disease.\emph{Annals of Otology, Rhinology \& Laryngology} , \emph{100}
(6), 464--468. https://doi.org/10.1177/000348949110000607

\textbf{9-} Chuang, K.-F., Liu, F.-C., \& Chen, H.-C. (2021). Bilateral
sudden sensorineural hearing loss in patient with Behçet
disease.\emph{Ear, Nose \& Throat Journal} , 014556132110516.
https://doi.org/10.1177/01455613211051660

\textbf{10-} Berrettini, S., Bruschini, P., Sellari Franceschini, S.,
Mita, L., Olivieri, I., \& Gemignani, G. (1989). {[}Sudden deafness and
Behçet's disease{]}. \emph{Acta Oto-Rhino-Laryngologica Belgica}
,\emph{43} (3), 221--229.

\textbf{11-} Adler, Y. D., Jovanovic, S., Jivanjee, A., Krause, L., \&
Zouboulis, C. C. (n.d.). Adamantiades-Behçet's disease with inner ear
involvement. \emph{Clinical and Experimental Rheumatology} , \emph{20}
(4 Suppl 26), S40-2.

12-Sfikakis, P. P., Markomichelakis, N., Alpsoy, E., Assaad-Khalil, S.,
Bodaghi, B., Gul, A., Ohno, S., Pipitone, N., Schirmer, M., Stanford,
M., Wechsler, B., Zouboulis, C., Kaklamanis, P., \& Yazici, H. (2007).
Anti-TNF therapy in the management of Behcet's disease--review and basis
for recommendations. \emph{Rheumatology} , \emph{46} (5), 736--741.
https://doi.org/10.1093/rheumatology/kem034

\textbf{Figures and tables:}

Table.1 Laboratory blood tests\selectlanguage{english}
\begin{longtable}[]{@{}lll@{}}
\toprule
Laboratory test & Result & Normal value\tabularnewline
\midrule
\endhead
White blood cell count & 9.4 * 10\^{}3 /uL & (4 -- 10) * 10\^{}3
/uL\tabularnewline
Hemoglobulin & 15.4 gm/dl & (13- 17) gm/dl\tabularnewline
Platelet & 336 * 10\^{}3 /uL & (150 -- 400) * 10\^{}3 /uL\tabularnewline
Urea & 4.8 mmol/L & (3.2 -- 7.4) mmol/L\tabularnewline
Creatinine & 86 umol/L & (64- 110) umol/L\tabularnewline
HbA1C \% & 5.4 \% & 4.8- 5.9 \%\tabularnewline
C- reactive protein & 17 mg/L & (0 -5) mg/L\tabularnewline
Antinuclear antibody (ANA) & Negative & Negative\tabularnewline
Antineurtrophil Cytoplasmic Antibody (ANCA) & Negative &
Negative\tabularnewline
Anti-Cardiolipin antibody IgM \& IgG antibodies & Negative &
Negative\tabularnewline
Ani- B2 glycoprotein IgM \& IgG antibodies & Negative &
Negative\tabularnewline
Treponema Pallidum antibody & Negative & Negative\tabularnewline
QuantiFERON TB plus & Negative & Negative\tabularnewline
HLA -- B51 typing & Negative & Negative\tabularnewline
\bottomrule
\end{longtable}

Figure 1: A pure tone audiogram showed bilateral sensorineural hearing
loss more on high frequencies\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

\end{center}
\end{figure}

Figure
2. MRI sections of head and internal auditory meatus.

\textbf{ACKNOWLEDGMENT}

The authors would like to acknowledge Qatar national library (QNL) for
this publication's funding and the HMC internal medicine residency
program for scientific support.

\textbf{CONSENT}

Written informed consent was obtained from the patient for the
publication of this case report

\textbf{CONFLICT OF INTEREST}

The authors have no conflict of interest to declare.

\textbf{DATA AVAILABILITY STATEMENT}

Available upon request

\textbf{Authors contribution:}

Mohanad Faisal: manuscript writing, literature review, application

Haydar Barjas: manuscript writing, literature review.

Wisam Alwassiti: manuscript writing, literature review.

Walid Omer: manuscript writing, literature review, clinical follow-up.

Nabeel Abdulla: manuscript writing, literature review, clinical
follow-up

\selectlanguage{english}
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\end{document}

