Behcet disease: Do individual symptomatology or certain drug intake reflect the severity of sensory neural hearing loss?

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Dina Osman, Mervat Bahiri, Noha Hassan, Yumn Elsabbagh This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5509871/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract Background: Behcet disease is a relapsing, chronic, systemic inflammatory illness characterized by mucocutaneous, articular, neurological, urogenital, vascular, intestinal, and pulmonary symptoms in addition to recurrent aphthous stomatitis, genital ulcerations, and ophthalmic disease. Objectives: Assessing effect of disease symptomatology, drugs used on sensorineural hearing loss severity. Methods: In this study, sixty adult Behcet disease patients participated. All underwent a comprehensive medical history, a basic audiological assessment, a Behcet disease current activity form, and a tinnitus handicap inventory scale. Results: 60% of the participants, had sensorineural hearing loss; over half (55.6%) had mild sensorineural hearing loss, there is no statistically significant correlation between the duration, the Behcet disease current activity form score, the tinnitus handicap inventory scale, vascular symptoms, and sensorineural hearing loss. Conclusions: prevalence of sensorineural hearing loss is 60%. Auditory manifestations and HB level are independent factors for SNHL, no relation between disease manifestation, duration, disease activity, drugs and severity of hearing loss, no relation between level of platelets, HB, TLC, CRP, ESR and severity of hearing loss. Behcet disease sensorineural hearing loss Behcet disease current activity form Main points This study is a cross sectional study on sixty patients diagnosed with Behcet disease, showing that Behcet disease is more common in males than females. Prevalence of SNHL was 60% among patients included in this study and there was a significantly higher proportion of hearing loss among males than among females. All patients with neuro-Behcet had SNHL Auditory manifestation and severity of SNHL were variable among patients with increase severity in older age. No significant correlation between disease symptoms or used medications and the severity of sensorineural hearing loss. Introduction A widespread vasculitis of the small, medium, and large vessels (arteries and veins) is the hallmark of Behçet disease, a complex multisystem illness (1) . It is an inflammatory, chronic, and recurrent illness that affects the vascular, central nervous, mucocutaneous, and ocular systems (2). According to the International Study Group for Behçet's Disease, oral aphthae must coexist with two of the following conditions: genital aphthae, skin lesions (such as acneiform nodules, erythema nodosum, pseudo folliculitis, or papulopustular lesions), eye lesions (such as uveitis or retinal vasculitis), or a positive pathergy test (3) . Patients with Behcet disease are more likely to experience hearing loss; inner ear affliction may be caused by injury to the outer hair cells in the cochlea or by vasculitis affecting the labyrinthine arteries or its branch, the common cochlear artery. Sensorineural hearing loss, particularly in the moderate to high frequencies, is a complication of Behcet disease. Incidence of hearing impairment in BD ranges from 24 to 62% (4–7) . Hearing loss occurs more frequently than vestibular affection. Three to twenty-five percent of patients with Behçet's disease have neurological symptoms. The majority of neurological symptoms are either secondary to significant vascular involvement or result from primary neural parenchymal lesions. The inflammatory cellular infiltration of mononuclear cells surrounding small blood vessels is represented by parenchymal lesions. Excessive gliosis and atrophy become more noticeable in chronic situations (7, 8). The BD causes parenchymal lesions such as brainstem, cerebellum encephalitis, pseudotumors and myelitis, while extra-parenchymal lesions include cerebral venous thrombosis and arterial aneurysm. These lesions may be associated with few-symptomatic meningitis in about 70% of cases. The main symptoms are brainstem lesions such as sensori-motor deficiencies, cranial nerve palsies and sphincter dysfunctions; however, headache, confusion, personality changes and memory loss are also common symptoms. Psychiatric symptoms and cognitive impairment are frequent in BD (8, 9). The most frequent imaging findings in the acute stage are extensive lesions in the brainstem or basal ganglia that can spread to the diencephalon. Typically, parenchymal lesions present as a brain-stem syndrome characterized by pyramidal abnormalities, ataxia, cognitive impairment, and sphincter dysfunction. In addition to having a chronic course with potential permanent neurological impairments, BD has a relapsing and remitting course with multifocal neurological involvement (7, 8) . Clinical signs of non-parenchymal involvement in patients include elevated intracranial pressure due to obstruction of the dural sinus or, in rare cases, an arterial stroke syndrome. Few researches have demonstrated how attention, working memory, retrieval skills, and executive processes are impacted by BD, and the effects of BD on higher cognitive functions are still not well understood (9). A rapid hearing loss of 30 dB at three consecutive frequencies in three days is known as sudden sensorineural hearing loss (SSNHL). There are 5 to 20 cases of SSNHL for every 100,000 individuals annually. However, only 10% to 15% of patients have a documented cause for SSNHL; the rest cases are classified as idiopathic. Viral infection, vascular disruption, stress-mediated response, inner ear membrane rupture, and immune-mediated illness are some possible causes of idiopathic SSNHL (8) . Few cases of SSNHL among Behcet disease patients have been documented due to the immunologic mechanisms underlying the genesis of SSNHL and the fact that BD is an autoimmune disease. Currently, no evidence-based treatment is available for SSNHL; steroids are clinically recommended either systemically or intra-tympanic steroid injection (ITSI), also hyperbaric oxygen therapy (HBOT), and acupuncture may improve prognosis (9) . Aim of the study: Current study aimed at evaluation of disease symptomatology and drugs effect on sensorineural hearing loss in adult BD patients. Patients and Methods Subjects: The study was designed as a cross sectional study conducting on sixty patients diagnosed with Behcet disease that was conducted from April 2023 to April 2024. Informed consent was obtained from all participants. Research protocol was approved by the XXX Research Ethics Committee, the approval number: (MS-258-2023). It included 60 adult subjects of both genders that were co-operative, alert and of average intelligence that were able to understand and perform tests, fulfilling the inclusion criteria. Inclusion criteria of study group: Patients fulfil Diagnostic criteria published by the International Study Group for Behçet’s disease (3). Age between 18-55 years. Both genders are involved. Exclusion criteria of study subjects: Individuals age less than 18 years or more than 55 years. History or presence of any other otological or neuromuscular diseases. Abnormal tympanometry. History of ear trauma or surgery. History of ototoxic medications. Patients with hypertension, and diabetes mellitus. Autoimmune disease other than Behcet disease. Smokers. Methodology: Equipments: Sound treated room (Amplisilence Model E). Tympanometry: Zodiac 901 (Madsen Corporation, USA). callibrated according ISO standards. Pure tone audiometer: Itera II, Madsen Otometrics (GN Otometrics, Denmark) calibrated according to International Standard Organization (ISO) standards.TDH-39 head phones and radio-ear B-71 bone vibrator was used. TEOAEs: Neuro-Audio (Neurosoft Ltd, Russia. Ivanovo), with ER-3A insert earphones. Procedure: All subjects in this study were subjected to the following: A) Full history taking: including; including the age, sex, residency, disease manifestation and duration. B) Disease activity according to Behcet Disease Current Activity Forum (BDCAF): The BDCAF was used, scores oral and genital ulceration, skin, joint and gastrointestinal involvement, presence of fatigue and headache, large-vessel and central nervous system (CNS) involvement and Eye activity in form of blurring of vision or if the eye was painful or red in the last 4 weeks (10) . C) Otological examination: to exclude any external or middle ear pathologies. D) Basic Audiological Assessment, including: Extended pure tone audiometry (PTA) : for octave frequencies 250-10000 Hz for air conduction and 500-4000Hz for bone conduction, using pulsed stimulus. Speech reception threshold (SRT ): using Arabic spondaic words . Word discrimination score (WDS ), using Arabic phonetically balanced words (11). Immittancemetry: single-frequency tympanometry with a probe tone of 226 Hz with testing of the acoustic reflex threshold (ipsilateral and contralateral) at frequencies 500, 1000, 2000 and 4000 Hz. E) Tinnitus Handicap Inventory (THI): THI was used to assess tinnitus annoyance levels. It consists of 25 questions divided into three categories: functional, emotional, and catastrophic. There are three possible response options for each question; yes (4 points), sometimes (2 points), or not at all (no points). Handicap severity categories for the Tinnitus Handicap Inventory according to (Newman et al., 1998) (12) : □ No handicap: scoring range: 0 to16 in the total THI score. □ Mild handicap: scoring range: 18 to 36 in the total THI score. □ Moderate handicap: scoring range: 38 to 56 in the total THI score. □ Severe handicap: scoring range: 58 to 100 in the total THI score. F) Transient otoacoustic emissions (TEOAEs): Transient evoked otoacoustic emissions (TEOAEs) were measured using a 100μs click stimulus at 80 dBSPL, band pass filtered 0.3 to 5 kHz, at a rate of 66 Hz. Noise level was below 50 dB SPL. 1000 averages were collected to judge the response. Responses were recorded in two buffers (A & B) and averaged separately. The average amplitude of these two waveforms presented the overall echo level in dBSPL. The software determined the amplitude of TEOAE in five frequency bands (1, 2, 3, 4, and 5 kHz). Signal to noise ratio (SNR) was computed for each frequency band. In addition, the reproducibility of the TEOAE was tested by the correlation between the signals from the two buffers. All responses were stored for analyses. TEOAE were considered present if the whole reproducibility was 50 % according to Kemp, 2002 . The pass criteria were response SNR ≥4 dB with reproducibility ≥70% in at least three frequencies with overall SNR ≥ 6 dB and overall reproducibility ≥ 70%. A partial pass criterion was if the whole reproducibility was 50–70%. G) Labs assessment: Complete blood count Inflammatory markers in form of ESR, CRP Statistical methods: Based on evidence from previous similar study and by considering the prevalence of sensorineural hearing loss in behcet disease as a primary outcome, epi-calc 2000 was used to calculate the sample size of this study. Assuming 805 power and 0.05 level of significance 76% proportion of cases exposed, to detect odd ratios OR=6. Sample size will be 54. Considering drop out rates of 10%, the final sample size should be 60 participants. Data were analyzed using SPSS statistical package version 28. The normality of the data was tested using the Kolmogorov-Smirnov single-sample test. Qualitative data are described as median (range). Relation between qualitative data was done using the Chi-square test. Numerical variables were presented as median (range). The comparison between the two groups of numerical was done using the Mann-Whitney test. Logistic regression was applied to calculate the odds ratio (OR), and its 95% confidence intervals (CI) were calculated to estimate the risk. Significant factors affecting hearing loss (at p-value 0.1) on univariate analysis were entered in multivariate analysis using the stepwise logistic regression method. Spearman correlation was used to correlate continuous data. A probability (p-value) equal to or less than 0.05 is considered significant. Results The study included 60 patients diagnosed with Behect disease; the median age of the participants was 33 years, ranging from (19-53 years). The majority of the participants (86.7%) were males. The median disease duration was 5 years, ranging from (0.5-22 years). The most frequent dermatological manifestation was recurrent oral and genital ulcers. Neurological manifestation occurred in 13.3% of the participants. About one-fourth of the participants (26.7%) complained of auditory manifestation, all of them had gradual hearing loos onset and 30% of the patients had vascular manifestations. Nearly one-third of the participants (33.3%) had locomotor manifestation, and three-fourths of the patients had ocular manifestation as illustrated in table 1. As shown in table 2, about two-thirds (60%) of the participants had sensorineural hearing loss. Among participants with hearing loss, more than half of the participants with hearing loss (55,6%) had mild sensorineural hearing loss, however around 33% had moderate sensorineural hearing loss and 11% had severe hearing loss. Regarding transient evoked optoacoustic emissions (TEOAE) less than half of the participants (48.3%) had passed right TEOAE and 41.7% had passed left TEOAE. Fifty-one patients were on prednisolone, 31 on colchicine, 30 on azathioprine, 15 on cyclosporine, 13 on Anti-TNF, 2 on mycophenolate, 7 on cyclophosphamide and only 1 patient on rituximab, as shown in table 3. There was no statistically significant difference between any drug used by participants and sensorineural hearing loss, table 4. Although 50 patients were on combined drugs regimen and 10 patients on single drug regimen, it was found to be not statistically significant. As shown in table 5, all patients with Neuro Behcet Disease had sensorineural hearing loss detected by PTA. Among 16 patients of auditory manifestations, 13 patients (81.3%) had SNHL detected by PTA. Among 44 patients of no auditory manifestations, 23 patients (52.3%) had positive SNHL detected by PTA. No statistically significant relation between disease duration, BDCAF score, vascular manifestations, tinnitus handicap inventory scale and sensorineural hearing loss detected by PTA, P value (0.943, 0.119, 0.908, 0.376 respectively). The median Hemoglobin level was 13.6, ranging from (9.7-16), the median Platelet level was 250.5, ranging from (123-655), the median ESR was 15, ranging from (3-100), and the median CRP was 7, ranging from (1-120), table 6. As shown in table 7, There was correlation between higher average hemoglobin level among patients with sensorineural hearing loss than among those without sensorineural hearing loss (p value=0.041). No statistically significant difference between levels of Platelet, TLC, ESR, CRP and sensorineural hearing loss No statistically significant difference was found between disease characteristics, symptoms, tinnitus handicap inventory scale and severity of hearing loss among the participants, there was no statistically significant difference between any drug used by participants and severity of hearing loss, also; there was no statistically significant difference in Hemoglobin¸ Platelet, TLC, ESR¸CRP and severity of hearing loss (table 8). Table 9 shows the multivariate analysis of factors associated with sensorineural hearing loss. The factors independently affecting hearing loss were auditory manifestation and higher Haemoglobin level. To sum up the results, the prevalence of SNHL was 60% of the participants by PTA, among them, more than half of the participants (55,6%) had mild sensorineural hearing loss with a significantly higher proportion of hearing loss among males than among females (67.3% versus 12.5%, p-value =.005). All patients with PNBD had sensorineural hearing loss. Among 16 patients of auditory manifestations, 13 patients (81.3%) had SNHL detected by PTA. Among 44 patients of no auditory manifestations, 23 patients (52.3%) had positive SNHL detected by PTA. No statistically significant relation between disease duration, BDCAF score, vascular manifestations, THI and SNHL. No statistically significant relation between BD treatment and SNHL. Auditory manifestations were associated significantly with higher Hemoglobin level (p- value 0.245) and higher age (p- value 0.041). Discussion Mucocutaneous lesions, ocular, vascular, articular, neurologic, gastrointestinal, urogenital, pulmonary, and cardiac involvement are among the clinical manifestations of Behcet disease (BD). BD is a chronic, recurring, inflammatory disease whose cause is unknown. Despite being widespread, "Silk Road" towns are where the disease is most prevalent. The more severe course of BD is more likely to affect younger people and men. It has an autoimmune etiology in genetically predisposed people after exposure to specific environmental triggers or viral factors (13). This cross-sectional study, which involved sixty patients with Behcet disease diagnoses, sought to determine the features of hearing loss in these patients as well as explore the association between the likelihood of hearing loss and variables such as other system involvements, patient age and gender, disease duration, used medications and tinnitus assessment in Behcet disease patients. Males made up the bulk of participants in this study (86.7%), with a female to male ratio of 1:6.5. It seems that regional variations exist in the distribution of genders. The under-diagnosis of BD in females resulting from some ethnic groups' reluctance to acquire a diagnosis could be the explanation of the predominance of BD in males in emerging countries. Recurrent oral and genital ulcers were the most prevalent dermatological symptom. This is in line with the findings of Alposy et al., who reported that the most frequent symptom was genital and mouth ulcers (14). According to Azizlerli et al., the most frequent mucocutaneous signs were recurring oral and genital ulcers, which were followed by papulopustular lesions, erythema nodosum, and thrombophlebitis (15). The prevalence of the pathergy test was 16.7% in our study, which was lower than the prevalence of positive pathergy test in Tursen et al. (16) and Houman et al. (17) research involving 56.1% and 62.4% of Behcet patients, respectively. The variation in methods used by the teams to conduct the pathergy test and the use of colchicine or anti-inflammatory medications prior to the test can both account for the results' dispersion. Although some BD patients manifest with sudden SNHL, but one-fourth of our participants (26.7%) complained of auditory manifestation (tinnitus and diminution hearing) all with gradual onset, representing the fifth manifestation of Behcet after mucocutaneous, ocular, locomotor and vascular, whereas it has been reported to be after oral and genital ulcers, and skin lesions in the study performed by El Menyawi et al. (18). It was discovered that almost two thirds (60%) of the participants had sensorineural hearing loss (SNHL) after employing PTA to evaluate our patients. Of the 44 individuals who did not exhibit any auditory symptoms, 23 (52.3%) had positive SNHL found by PTA; of the participants who did have hearing loss, over half (55.6%) had mild sensorineural hearing loss. This was in line with the findings of Gemignani et al., who found that 60% of patients with Behcet disease had hearing loss. One third of the participant had unilateral hearing loss, while two thirds had bilateral hearing loss. The audiological evaluation revealed moderate to severe sensorineural hearing loss (>35 dB) in at least two frequencies (19). While Abdel Baki et al where SNHL was found in 28% ranging in degree from mild to severe. Behcet disease may be the cause of sensorineural hearing loss, particularly in the moderate to high frequencies, as vasculitis damages the outer hair cells in the cochlea or affects the labyrinthine vasculature or its branch, the common cochlear artery (20). As a result of the male preponderance of Behcet illness, Cinar et al. observed that the prevalence of SNHL in the Behcet group was substantially greater in men than in women, which is consistent with our findings (21). The age of the patient, the duration of the disease, used medications and sensorineural hearing loss were not found to be significantly correlated in the current study. This is in line with the findings of Mahdi et al., who reported that 59.26% of Behcet patients had a typical audiogram with bilateral high-frequency SNHL, with a down slope was the most common pattern (22, 23) . These findings disagreed with those of Karadağ et al., who reported that 70,6% of BD patients had SNHL and that the mean age of those patients was higher than that of those with BD who did not have SNHL. Additionally, it was found that patients with BD and SNHL had longer disease durations than patients without SNHL (24). Our study found that all patients with Neuro-BD had sensorineural hearing loss, which is inconsistent with Cinar et al.'s findings that 68.3% of neuro-BD patients had SNHL. There was also no statistically significant correlation found between hearing loss and other system involvements or with a positive pathergy test. However, we did not find a statistically significant difference between vascular symptoms and hearing loss, in line with Cinar et al. (21). We discovered that among the clinical manifestations, auditory manifestation had an independent effect on hearing loss. This finding contradicted the findings of Kemal et al., who found that 34,5% of BD patients had SNHL, especially at higher frequencies, and that none of the Behcet disease patients had any complaints regarding their hearing. This may be because none of them experienced a severe or profound loss, merely mild or moderate impairment (25). No statistically significant difference between different treatment used by participants (colchicine, prednisolone, anti- TNF, azathioprine, cyclosporine, mycophenolate, cyclophosphamide, rituximab) and sensorineural hearing loss or its severity among the treatment assessment of our patients. This is consistent with Cinar et al that reported colchicine use had no effect on the prevalence of SNHL in Behcet group (21) . Some controversial reports have been reported on the effect of cyclosporine on hearing loss. For example, Elidan et al found that it resulted in significant hearing improvement, while Soylu et al observed no improvement (26, 27). There is no statistically significant correlation found in this study between sensorineural hearing loss, tinnitus handicap inventory scale, and BDCAF score. Although there was no statistically significant difference between the participants' tinnitus handicap questionnaire score, disease characteristics, symptoms, or severity of hearing loss, we did find that patients with moderate to severe hearing loss were substantially older than patients with mild hearing loss. Limitations: This study's primary limitation is its cross-sectional design, which lacks causality and means that conclusions should currently be interpreted in terms of associations. Additionally, because of the study's small patient population, more patient studies are required to confirm the findings, and there is no control group to compare the prevalence of SNHL between normal and BD. Recommendations: We recommend a cohort study with follow up of patients to assess prevalence of SNHL using longitudinal data, also it is recommended to involve larger number of patients.The findings of the present study demonstrated that audiological involvement is more frequent in patients with Behcet disease. Therefore, all patients with Behcet disease especially with neurological manifestations should be regularly monitored by an audiologist and be given information about the possibility of inner-ear involvement. All patients with hearing loss were rehabilitated by the audiology consultant and were instructed for hearing aid fitting, avoid ototoxic drugs, and avoid noise exposure and regular follow up with pure tone audiometry assessment every 6 months. Regarding patients suffered from tinnitus they were instructed for sound therapy by the audiology consultant. Conclusion This cross-sectional study, which included sixty patients with Behcet disease diagnoses, revealed that males were more likely than females to have the condition. The study found that all patients with neuro-Behcet had SNHL, the median age was 33 years, the prevalence of SNHL was 60%, the proportion of hearing loss in males was considerably higher than in females, the auditory presentation and severity of SNHL varied among individuals, and the severity increased with age. Auditory manifestations and HB level are independent factors for SNHL, no relation between disease manifestation, disease duration, disease activity, disease treatment and severity of SNHL, no relation between level of platelets, TLC, CRP, ESR and severity of SNHL and no relation between level of platelets, HB, TLC, CRP, ESR and severity of SNHL. Declarations Ethics approval: Research protocol was approved by the XXX Research Ethics Committee, the approval number: (MS-258-2023). Consent to participate: Informed consents were taken from all participants in this research. Consent for publication: Not applicable. Availability of data and material: Available upon request. Competing interests: No competing interests. Funding: Not applicable. Acknowledgements: Not applicable. Clinical trial number: Not applicable. References Hirohata S, Kikuchi H. (2003): Behçet’s disease. Arthritis Res Ther; 5 (3):139-4. Ahmet Karadağ , Mujde Karadağ , Adem Bora , Emrullah Hayta , A.Bahadır Çetin , Sevil C. Doğan , Kasım Durmuş & E. Elif Altuntaş. (2019): evaluation of hearing loss and tinnitus in behcet’s disease, European Archives of Oto-Rhino-Laryngology volume 276, pages2691–2696. International Study Group for Behçet’s Disease. (1990): Criteria for diagnosis of Behçet’s disease. Lancet; 335 (8697):1078-80. Mancini P, Atturo F, Di Mario A, Portanova G, Ralli M, De Virgilio A, et al. (2018): Hearing loss in autoimmune disorders: prevalence and therapeutic options. 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A., & Hamdy, M. M. (2021). Cervical vestibular evoked myogenic potential and high-frequency audiometry results in Behçet’s disease. Egyptian Rheumatology and Rehabilitation, 48(3), 1-9. Cinar, S., Cinar, F., & Kiran, S. (2012). Is there a need for audiologic evaluation in patients with Behçet disease? Ear Nose Throat J. 91(3):15-19. Mahdi, B., Mehdi, G. M., Reza, H. M., Mahdieh, T., & Taghi, S. M. (2007a). Hearing loss in Behçet syndrome. Otolaryngology - Head and Neck Surgery, 137(3), 439–442. Mahdi, B., Mehdi, G. M., Reza, H. M., Mahdieh, T., & Taghi, S. M. (2007b). Hearing loss in Behçet syndrome. Otolaryngology - Head and Neck Surgery, 137(3), 439–442. Karadağ, A., Karadağ, M., Bora, A., Hayta, E., Çetin, A. B., Doğan, S. C., Durmuş, K., & Altuntaş, E. E. (2019). Evaluation of hearing loss and tinnitus in Behcet’s disease. European Archives of Oto-Rhino-Laryngology, 276(10), 2691–2696. Kemal O, Anadolu Y, Boyvat A, Tatarağası A. (2013). Behçet disease as a cause of hearing loss: A prospective, placebo-controlled study of 29 patients. Ear Nose Throat J. 92(3):112-120. Elidan J, Levi H, Cohen E, BenEzra D. (1991). Effect of cyclosporine A on the hearing loss in Behçet’s disease. Annals of Otology, Rhinology & Laryngology, 100(6):464-468. Soylu L, Aydoğan B, Soylu M, Ozsahinoğlu C. (1995). Hearing loss in Behçet’s disease. Annals of Otology, Rhinology & Laryngology, 104(11):864-867. Tables Tables 1 to 9 are available in the Supplementary Files section. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5509871","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":434399092,"identity":"d075f9de-8b55-4130-b3b2-aa2c397975cf","order_by":0,"name":"Dina Osman","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABA0lEQVRIiWNgGAWjYDCCw0BcAWIcAHNtgJi5AcbDreUMQksaAwMbIwEtB1C1HCashe8478EPByoOy/Mdb3+64eeO83IG9xsbH3w4wyDPL4Zdn+RhvmSJA2cOG848c8bsZu+Z28YGxxibDWfcYDCcOTsBqxaDwzwG0h/bDjNuuJHDdoO37XbihmOMbdI8HxgSDG7j1GL842DbYfsNN9Kf3fzbdo4oLWYSQC2JG24kmN3mbTsA1XIDtxZJoBaLA2fSk0F+uS3blmwseSwR6JczEjj9wnf+jPGNAxXWtn3H25/dfNtmJ8d3+PDBBx+O2cjzS2PXghNIkKZ8FIyCUTAKRgEKAAC9PXEbwxHrFAAAAABJRU5ErkJggg==","orcid":"","institution":"Cairo University","correspondingAuthor":true,"prefix":"","firstName":"Dina","middleName":"","lastName":"Osman","suffix":""},{"id":434399093,"identity":"8cb21369-87d9-469c-b4f0-582534990291","order_by":1,"name":"Mervat Bahiri","email":"","orcid":"","institution":"Cairo University","correspondingAuthor":false,"prefix":"","firstName":"Mervat","middleName":"","lastName":"Bahiri","suffix":""},{"id":434399094,"identity":"f92cb4bf-a0b1-4e07-8ed5-10652c1f8812","order_by":2,"name":"Noha Hassan","email":"","orcid":"","institution":"Cairo University","correspondingAuthor":false,"prefix":"","firstName":"Noha","middleName":"","lastName":"Hassan","suffix":""},{"id":434399095,"identity":"e8725379-76ee-49a3-87db-21682ba57643","order_by":3,"name":"Yumn Elsabbagh","email":"","orcid":"","institution":"Cairo University","correspondingAuthor":false,"prefix":"","firstName":"Yumn","middleName":"","lastName":"Elsabbagh","suffix":""}],"badges":[],"createdAt":"2024-11-23 12:08:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5509871/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5509871/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":79340062,"identity":"874153c8-66b1-477b-881a-ddfe28e85709","added_by":"auto","created_at":"2025-03-27 08:31:34","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":900411,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5509871/v1/b06fcb5f-505e-4606-8579-7625ae518a81.pdf"},{"id":79338219,"identity":"84ac9982-d0c3-4c90-ab39-96b1e0271ad7","added_by":"auto","created_at":"2025-03-27 08:15:34","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":35249,"visible":true,"origin":"","legend":"","description":"","filename":"Tables.docx","url":"https://assets-eu.researchsquare.com/files/rs-5509871/v1/663c32f0688452c11978a053.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Behcet disease: Do individual symptomatology or certain drug intake reflect the severity of sensory neural hearing loss?","fulltext":[{"header":"Main points","content":"\u003col\u003e\n \u003cli\u003eThis study is a cross sectional study on sixty patients diagnosed with Behcet disease, showing that Behcet disease is more common in males than females.\u003c/li\u003e\n \u003cli\u003ePrevalence of SNHL was 60% among patients included in this study and there was a significantly higher proportion of hearing loss among males than among females.\u003c/li\u003e\n \u003cli\u003eAll patients with neuro-Behcet had SNHL\u003c/li\u003e\n \u003cli\u003eAuditory manifestation and severity of SNHL were variable among patients with increase severity in older age.\u003c/li\u003e\n \u003cli\u003eNo significant correlation between disease symptoms or used medications and the severity of sensorineural hearing loss.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Introduction","content":"\u003cp\u003eA widespread vasculitis of the small, medium, and large vessels (arteries and veins) is the hallmark of Behçet disease, a complex multisystem illness \u003cstrong\u003e(1)\u003c/strong\u003e. It is an inflammatory, chronic, and recurrent illness that affects the vascular, central nervous, mucocutaneous, and ocular systems \u003cstrong\u003e(2).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAccording to the International Study Group for Behçet's Disease, oral aphthae must coexist with two of the following conditions: genital aphthae, skin lesions (such as acneiform nodules, erythema nodosum, pseudo folliculitis, or papulopustular lesions), eye lesions (such as uveitis or retinal vasculitis), or a positive pathergy test \u003cstrong\u003e(3)\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003ePatients with Behcet disease are more likely to experience hearing loss; inner ear affliction may be caused by injury to the outer hair cells in the cochlea or by vasculitis affecting the labyrinthine arteries or its branch, the common cochlear artery. Sensorineural hearing loss, particularly in the moderate to high frequencies, is a complication of Behcet disease. Incidence of hearing impairment in BD ranges from 24 to 62% \u003cstrong\u003e(4–7)\u003c/strong\u003e. Hearing loss occurs more frequently than vestibular affection.\u003c/p\u003e\n\u003cp\u003eThree to twenty-five percent of patients with Behçet's disease have neurological symptoms. The majority of neurological symptoms are either secondary to significant vascular involvement or result from primary neural parenchymal lesions. The inflammatory cellular infiltration of mononuclear cells surrounding small blood vessels is represented by parenchymal lesions. Excessive gliosis and atrophy become more noticeable in chronic situations \u003cstrong\u003e(7, 8).\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe BD causes parenchymal lesions such as brainstem, cerebellum encephalitis, pseudotumors and myelitis, while extra-parenchymal lesions include cerebral venous thrombosis and arterial aneurysm. These lesions may be associated with few-symptomatic meningitis in about 70% of cases. The main symptoms are brainstem lesions such as sensori-motor deficiencies, cranial nerve palsies and sphincter dysfunctions; however, headache, confusion, personality changes and memory loss are also common symptoms. Psychiatric symptoms and cognitive impairment are frequent in BD \u003cstrong\u003e(8, 9).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe most frequent imaging findings in the acute stage are extensive lesions in the brainstem or basal ganglia that can spread to the diencephalon. Typically, parenchymal lesions present as a brain-stem syndrome characterized by pyramidal abnormalities, ataxia, cognitive impairment, and sphincter dysfunction. In addition to having a chronic course with potential permanent neurological impairments, BD has a relapsing and remitting course with multifocal neurological involvement \u003cstrong\u003e(7, 8)\u003c/strong\u003e. Clinical signs of non-parenchymal involvement in patients include elevated intracranial pressure due to obstruction of the dural sinus or, in rare cases, an arterial stroke syndrome. Few researches have demonstrated how attention, working memory, retrieval skills, and executive processes are impacted by BD, and the effects of BD on higher cognitive functions are still not well understood \u003cstrong\u003e(9).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA rapid hearing loss of 30 dB at three consecutive frequencies in three days is known as sudden sensorineural hearing loss (SSNHL). There are 5 to 20 cases of SSNHL for every 100,000 individuals annually. However, only 10% to 15% of patients have a documented cause for SSNHL; the rest cases are classified as idiopathic. Viral infection, vascular disruption, stress-mediated response, inner ear membrane rupture, and immune-mediated illness are some possible causes of idiopathic SSNHL \u003cstrong\u003e(8)\u003c/strong\u003e. Few cases of SSNHL among Behcet disease patients have been documented due to the immunologic mechanisms underlying the genesis of SSNHL and the fact that BD is an autoimmune disease. Currently, no evidence-based treatment is available for SSNHL; steroids are clinically recommended either systemically or intra-tympanic steroid injection (ITSI), also hyperbaric oxygen therapy (HBOT), and acupuncture may improve prognosis \u003cstrong\u003e(9)\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAim of the study:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCurrent study aimed at evaluation of disease symptomatology and drugs effect on sensorineural hearing loss in adult BD patients.\u003c/p\u003e"},{"header":"Patients and Methods","content":"\u003cp\u003e\u003cstrong\u003eSubjects:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was designed as a cross sectional study conducting on sixty patients diagnosed with Behcet disease that was conducted from April 2023 to April 2024. Informed consent was obtained from all participants. Research protocol was approved by the XXX Research Ethics Committee, the approval number: (MS-258-2023).\u003c/p\u003e\n\u003cp\u003eIt included 60 adult subjects of both genders that were co-operative, alert and of average intelligence that were able to understand and perform tests, fulfilling the inclusion criteria.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInclusion criteria of study group:\u003c/strong\u003e\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003ePatients fulfil Diagnostic criteria published by the International Study Group for Beh\u0026ccedil;et\u0026rsquo;s disease \u003cstrong\u003e(3).\u003c/strong\u003e\u003c/li\u003e\n \u003cli\u003eAge between 18-55 years.\u003c/li\u003e\n \u003cli\u003eBoth genders are involved.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u003cstrong\u003eExclusion criteria of study subjects:\u003c/strong\u003e\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003eIndividuals age less than 18 years or more than 55 years.\u003c/li\u003e\n \u003cli\u003eHistory or presence of any other otological or neuromuscular diseases.\u003c/li\u003e\n \u003cli\u003eAbnormal tympanometry.\u003c/li\u003e\n \u003cli\u003eHistory of ear trauma or surgery.\u003c/li\u003e\n \u003cli\u003eHistory of ototoxic medications. \u0026nbsp;\u003c/li\u003e\n \u003cli\u003ePatients with hypertension, and diabetes mellitus.\u003c/li\u003e\n \u003cli\u003eAutoimmune disease other than Behcet disease.\u003c/li\u003e\n \u003cli\u003eSmokers.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u003cstrong\u003eMethodology:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEquipments:\u003c/strong\u003e\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003eSound treated room (Amplisilence Model E).\u003c/li\u003e\n \u003cli\u003eTympanometry: Zodiac 901 (Madsen Corporation, USA). callibrated according ISO standards.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cul\u003e\n \u003cli\u003ePure tone audiometer: Itera II, Madsen Otometrics (GN Otometrics, Denmark) calibrated according to International Standard Organization (ISO) standards.TDH-39 head phones and radio-ear B-71 bone vibrator was used.\u003c/li\u003e\n \u003cli\u003eTEOAEs: Neuro-Audio (Neurosoft Ltd, Russia. Ivanovo), with ER-3A insert earphones.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eProcedure:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll subjects in this study were subjected to the following:\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eA) Full history taking:\u0026nbsp;\u003c/strong\u003eincluding; including the age, sex, residency, disease manifestation and duration.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eB) Disease activity according to Behcet Disease Current Activity Forum (BDCAF):\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe BDCAF was used, scores oral and genital ulceration, skin, joint and gastrointestinal involvement, presence of fatigue and headache, large-vessel and central nervous system (CNS) involvement and Eye activity in form of blurring of vision or if the eye was painful or red in the last 4 weeks \u003cstrong\u003e(10)\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eC) Otological examination:\u003c/strong\u003e to exclude any external or middle ear pathologies.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eD) Basic Audiological Assessment, including:\u003c/strong\u003e\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003e\u003cem\u003e\u003cu\u003eExtended pure tone audiometry (PTA)\u003c/u\u003e\u003c/em\u003e: for octave frequencies 250-10000 Hz for air conduction and 500-4000Hz for bone conduction, using pulsed stimulus.\u003c/li\u003e\n \u003cli\u003e\u003cem\u003e\u003cu\u003eSpeech reception threshold (SRT\u003c/u\u003e\u003c/em\u003e\u003cem\u003e\u003cu\u003e):\u003c/u\u003e\u003c/em\u003e using Arabic spondaic words\u003cstrong\u003e.\u0026nbsp;\u003c/strong\u003e\u003cu\u003eWord discrimination score (WDS\u003c/u\u003e\u003cu\u003e),\u0026nbsp;\u003c/u\u003eusing Arabic phonetically balanced words \u003cstrong\u003e(11).\u003c/strong\u003e\u003c/li\u003e\n \u003cli\u003e\u003cem\u003e\u003cu\u003eImmittancemetry:\u003c/u\u003e\u003c/em\u003e single-frequency tympanometry with a probe tone of 226 Hz with testing of the acoustic reflex threshold (ipsilateral and contralateral) at frequencies 500, 1000, 2000 and 4000 Hz.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eE) Tinnitus Handicap Inventory (THI):\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTHI was used to assess tinnitus annoyance levels. It consists of 25 questions divided into three categories: functional, emotional, and catastrophic. There are three possible response options for each question; yes (4 points), sometimes (2 points), or not at all (no points). Handicap severity categories for the Tinnitus Handicap Inventory according to (Newman et al., 1998) \u003cstrong\u003e(12)\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003e□ No handicap: scoring range: 0 to16 in the total THI score.\u003c/p\u003e\n\u003cp\u003e□ Mild handicap: scoring range: 18 to 36 in the total THI score.\u003c/p\u003e\n\u003cp\u003e□ Moderate handicap: scoring range: 38 to 56 in the total THI score.\u003c/p\u003e\n\u003cp\u003e□ Severe handicap: scoring range: 58 to 100 in the total THI score.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eF) Transient otoacoustic emissions (TEOAEs):\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTransient evoked otoacoustic emissions (TEOAEs) were measured using a 100\u0026mu;s click stimulus at 80 dBSPL, band pass filtered 0.3 to 5 kHz, at a rate of 66 Hz. Noise level was below 50 dB SPL. 1000 averages were collected to judge the response. Responses were recorded in two buffers (A \u0026amp; B) and averaged separately. The average amplitude of these two waveforms presented the overall echo level in dBSPL. The software determined the amplitude of TEOAE in five frequency bands (1, 2, 3, 4, and 5 kHz). Signal to noise ratio (SNR) was computed for each frequency band.\u003c/p\u003e\n\u003cp\u003eIn addition, the reproducibility of the TEOAE was tested by the correlation between the signals from the two buffers. All responses were stored for analyses. TEOAE were considered present if the whole reproducibility was 50 % according to \u003cstrong\u003eKemp, 2002\u003c/strong\u003e. The pass criteria were response SNR \u0026ge;4 dB with reproducibility \u0026ge;70% in at least three frequencies with overall SNR \u0026ge; 6 dB and overall reproducibility \u0026ge; 70%. A partial pass criterion was if the whole reproducibility was 50\u0026ndash;70%.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eG) Labs assessment:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003eComplete blood count\u003c/li\u003e\n \u003cli\u003eInflammatory markers in form of ESR, CRP\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical methods:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBased on evidence from previous similar study and by considering the prevalence of sensorineural hearing loss in behcet disease as a primary outcome, epi-calc 2000 was used to calculate the sample size of this study. Assuming 805 power and 0.05 level of significance 76% proportion of cases exposed, to detect odd ratios OR=6. Sample size will be 54. Considering drop out rates of 10%, the final sample size should be 60 participants.\u003c/p\u003e\n\u003cp\u003eData were analyzed using SPSS statistical package version 28. The normality of the data was tested using the Kolmogorov-Smirnov single-sample test. Qualitative data are described as median (range). Relation between qualitative data was done using the Chi-square test. Numerical variables were presented as median (range). The comparison between the two groups of numerical was done using the Mann-Whitney test. Logistic regression was applied to calculate the odds ratio (OR), and its 95% confidence intervals (CI) were calculated to estimate the risk. Significant factors affecting hearing loss (at p-value 0.1) on univariate analysis were entered in multivariate analysis using the stepwise logistic regression method. Spearman correlation was used to correlate continuous data. A probability (p-value) equal to or less than 0.05 is considered significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe study included 60 patients diagnosed with Behect disease; the median age of the participants was 33 years, ranging from (19-53 years). The majority of the participants (86.7%) were males.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe median disease duration was 5 years, ranging from (0.5-22 years). The most frequent dermatological manifestation was recurrent oral and genital ulcers. Neurological manifestation occurred in 13.3% of the participants. About one-fourth of the participants (26.7%) complained of auditory manifestation, all of them had gradual hearing loos onset and 30% of the patients had vascular manifestations. Nearly one-third of the participants (33.3%) had locomotor manifestation, and three-fourths of the patients had ocular manifestation as illustrated in table 1.\u003c/p\u003e\n\u003cp\u003eAs shown in table 2, about two-thirds (60%) of the participants had sensorineural hearing loss. Among participants with hearing loss, more than half of the participants with hearing loss (55,6%) had mild sensorineural hearing loss, however around 33% had moderate sensorineural hearing loss and 11% had severe hearing loss.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRegarding transient evoked optoacoustic emissions (TEOAE) less than half of the participants (48.3%) had passed right TEOAE and 41.7% had passed left TEOAE.\u003c/p\u003e\n\u003cp\u003eFifty-one patients were on prednisolone, 31 on colchicine, 30 on azathioprine, 15 on cyclosporine, 13 on Anti-TNF, 2 on mycophenolate, 7 on cyclophosphamide and only 1 patient on rituximab, as shown in table 3. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThere was no statistically significant difference between any drug used by participants and sensorineural hearing loss, table 4. Although 50 patients were on combined drugs regimen and 10 patients on single drug regimen, it was found to be not statistically significant.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAs shown in table 5, all patients with Neuro Behcet Disease had sensorineural hearing loss detected by PTA. Among 16 patients of auditory manifestations, 13 patients (81.3%) had SNHL detected by PTA. Among 44 patients of no auditory manifestations, 23 patients (52.3%) had positive SNHL detected by PTA. No statistically significant relation between disease duration, BDCAF score, vascular manifestations, tinnitus handicap inventory scale and sensorineural hearing loss detected by PTA, P value (0.943, 0.119, 0.908, 0.376 respectively).\u003c/p\u003e\n\u003cp\u003eThe median Hemoglobin level was 13.6, ranging from (9.7-16), the median Platelet level was 250.5, ranging from (123-655), the median ESR was 15, ranging from (3-100), and the median CRP was 7, ranging from (1-120), table 6.\u003c/p\u003e\n\u003cp\u003eAs shown in table 7, There was correlation between higher average hemoglobin level among patients with sensorineural hearing loss than among those without sensorineural hearing loss (p value=0.041). No statistically significant difference between levels of Platelet, TLC, ESR, CRP and sensorineural hearing loss\u003c/p\u003e\n\u003cp\u003eNo statistically significant difference was found between disease characteristics, symptoms, tinnitus handicap inventory scale and severity of hearing loss among the participants, there was no statistically significant difference between any drug used by participants and severity of hearing loss, also; there was no statistically significant difference in Hemoglobin\u0026cedil; Platelet, TLC, ESR\u0026cedil;CRP and severity of hearing loss (table 8).\u003c/p\u003e\n\u003cp\u003eTable 9 shows the multivariate analysis of factors associated with sensorineural hearing loss. The factors independently affecting hearing loss were auditory manifestation and higher Haemoglobin level.\u003c/p\u003e\n\u003cp\u003eTo sum up the results, the prevalence of SNHL was 60% of the participants by PTA, among them, more than half of the participants (55,6%) had mild sensorineural hearing loss with a significantly higher proportion of hearing loss among males than among females (67.3% versus 12.5%, p-value =.005). All patients with PNBD had sensorineural hearing loss. Among 16 patients of auditory manifestations, 13 patients (81.3%) had SNHL detected by PTA. Among 44 patients of no auditory manifestations, 23 patients (52.3%) had positive SNHL detected by PTA. No statistically significant relation between disease duration, BDCAF score, vascular manifestations, THI and SNHL. No statistically significant relation between BD treatment and SNHL. Auditory manifestations were associated significantly with higher Hemoglobin level (p- value 0.245) and higher age (p- value 0.041).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eMucocutaneous lesions, ocular, vascular, articular, neurologic, gastrointestinal, urogenital, pulmonary, and cardiac involvement are among the clinical manifestations of Behcet disease (BD). BD is a chronic, recurring, inflammatory disease whose cause is unknown. Despite being widespread, \"Silk Road\" towns are where the disease is most prevalent. The more severe course of BD is more likely to affect younger people and men. It has an autoimmune etiology in genetically predisposed people after exposure to specific environmental triggers or viral factors\u003cstrong\u003e\u0026nbsp;(13).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis cross-sectional study, which involved sixty patients with Behcet disease diagnoses, sought to determine the features of hearing loss in these patients as well as explore the association between the likelihood of hearing loss and variables such as other system involvements, patient age and gender, disease duration, used medications and tinnitus assessment in Behcet disease patients.\u0026nbsp;\u003cbr\u003e\u0026nbsp;Males made up the bulk of participants in this study (86.7%), with a female to male ratio of 1:6.5. It seems that regional variations exist in the distribution of genders. The under-diagnosis of BD in females resulting from some ethnic groups' reluctance to acquire a diagnosis could be the explanation of the predominance of BD in males in emerging countries.\u003c/p\u003e\n\u003cp\u003eRecurrent oral and genital ulcers were the most prevalent dermatological symptom. This is in line with the findings of \u003cstrong\u003eAlposy et al.,\u003c/strong\u003e who reported that the most frequent symptom was genital and mouth ulcers \u003cstrong\u003e(14).\u0026nbsp;\u003c/strong\u003eAccording to \u003cstrong\u003eAzizlerli et al.,\u003c/strong\u003e the most frequent mucocutaneous signs were recurring oral and genital ulcers, which were followed by papulopustular lesions, erythema nodosum, and thrombophlebitis\u003cstrong\u003e\u0026nbsp;(15).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe prevalence of the pathergy test was 16.7% in our study, which was lower than the prevalence of positive pathergy test in \u003cstrong\u003eTursen et al. (16)\u003c/strong\u003e and \u003cstrong\u003eHouman et al. (17)\u003c/strong\u003e research involving 56.1% and 62.4% of Behcet patients, respectively. The variation in methods used by the teams to conduct the pathergy test and the use of colchicine or anti-inflammatory medications prior to the test can both account for the results' dispersion.\u003c/p\u003e\n\u003cp\u003eAlthough some BD patients manifest with sudden SNHL, but one-fourth of our participants (26.7%) complained of auditory manifestation (tinnitus and diminution hearing) all with gradual onset, representing the fifth manifestation of Behcet after mucocutaneous, ocular, locomotor and vascular, whereas it has been reported to be after oral and genital ulcers, and skin lesions in the study performed by \u003cstrong\u003eEl Menyawi et al. (18).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIt was discovered that almost two thirds (60%) of the participants had sensorineural hearing loss (SNHL) after employing PTA to evaluate our patients. Of the 44 individuals who did not exhibit any auditory symptoms, 23 (52.3%) had positive SNHL found by PTA; of the participants who did have hearing loss, over half (55.6%) had mild sensorineural hearing loss. This was in line with the findings of \u003cstrong\u003eGemignani et al.,\u003c/strong\u003e who found that 60% of patients with Behcet disease had hearing loss. One third of the participant had unilateral hearing loss, while two thirds had bilateral hearing loss. The audiological evaluation revealed moderate to severe sensorineural hearing loss (\u0026gt;35 dB) in at least two frequencies\u003cstrong\u003e\u0026nbsp;(19).\u003c/strong\u003e While \u003cstrong\u003eAbdel Baki et al\u003c/strong\u003e where SNHL was found in 28% ranging in degree from mild to severe. Behcet disease may be the cause of sensorineural hearing loss, particularly in the moderate to high frequencies, as vasculitis damages the outer hair cells in the cochlea or affects the labyrinthine vasculature or its branch, the common cochlear artery \u003cstrong\u003e(20).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAs a result of the male preponderance of Behcet illness,\u0026nbsp;Cinar et al.\u0026nbsp;observed that the prevalence of SNHL in the Behcet group was substantially greater in men than in women, which is consistent with our findings\u0026nbsp;(21).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe age of the patient, the duration of the disease, used medications and sensorineural hearing loss were not found to be significantly correlated in the current study. This is in line with the findings of \u003cstrong\u003eMahdi et al.,\u0026nbsp;\u003c/strong\u003ewho reported that 59.26% of Behcet patients had a typical audiogram with bilateral high-frequency SNHL, with a down slope was the most common pattern \u003cstrong\u003e(22, 23)\u003c/strong\u003e. These findings disagreed with those of \u003cstrong\u003eKaradağ et al.,\u003c/strong\u003e who reported that 70,6% of BD patients had SNHL and that the mean age of those patients was higher than that of those with BD who did not have SNHL. Additionally, it was found that patients with BD and SNHL had longer disease durations than patients without SNHL\u003cstrong\u003e\u0026nbsp;(24).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur study found that all patients with Neuro-BD had sensorineural hearing loss, which is inconsistent with \u003cstrong\u003eCinar et al.'s\u003c/strong\u003e findings that 68.3% of neuro-BD patients had SNHL. There was also no statistically significant correlation found between hearing loss and other system involvements or with a positive pathergy test. However, we did not find a statistically significant difference between vascular symptoms and hearing loss, in line with \u003cstrong\u003eCinar et al. (21).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe discovered that among the clinical manifestations, auditory manifestation had an independent effect on hearing loss. This finding contradicted the findings of \u003cstrong\u003eKemal et al.,\u0026nbsp;\u003c/strong\u003ewho found that 34,5% of BD patients had SNHL, especially at higher frequencies, and that none of the Behcet disease patients had any complaints regarding their hearing. This may be because none of them experienced a severe or profound loss, merely mild or moderate impairment \u003cstrong\u003e(25).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo statistically significant difference between different treatment used by participants (colchicine, prednisolone, anti- TNF, azathioprine, cyclosporine, mycophenolate, cyclophosphamide, rituximab) and sensorineural hearing loss or its severity among the treatment assessment of our patients. This is consistent with \u003cstrong\u003eCinar et al\u003c/strong\u003e that reported colchicine use had no effect on the prevalence of SNHL in Behcet group \u003cstrong\u003e(21)\u003c/strong\u003e. Some controversial reports have been reported on the effect of cyclosporine on hearing loss. For example, \u003cstrong\u003eElidan et al\u003c/strong\u003e found that it resulted in significant hearing improvement, while \u003cstrong\u003eSoylu et al\u003c/strong\u003e observed no improvement \u003cstrong\u003e(26, 27).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere is no statistically significant correlation found in this study between sensorineural hearing loss, tinnitus handicap inventory scale, and BDCAF score. Although there was no statistically significant difference between the participants' tinnitus handicap questionnaire score, disease characteristics, symptoms, or severity of hearing loss, we did find that patients with moderate to severe hearing loss were substantially older than patients with mild hearing loss.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLimitations:\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis study's primary limitation is its cross-sectional design, which lacks causality and means that conclusions should currently be interpreted in terms of associations. Additionally, because of the study's small patient population, more patient studies are required to confirm the findings, and there is no control group to compare the prevalence of SNHL between normal and BD.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRecommendations:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe recommend a cohort study with follow up of patients to assess prevalence of SNHL using longitudinal data, also it is recommended to involve larger number of patients.The findings of the present study demonstrated that audiological involvement is more frequent in patients with Behcet disease. Therefore, all patients with Behcet disease especially with neurological manifestations should be regularly monitored by an audiologist and be given information about the possibility of inner-ear involvement. All patients with hearing loss were rehabilitated by the audiology consultant and were instructed for hearing aid fitting, avoid ototoxic drugs, and avoid noise exposure and regular follow up with pure tone audiometry assessment every 6 months. Regarding patients suffered from tinnitus they were instructed for sound therapy by the audiology consultant.\u0026nbsp;\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis cross-sectional study, which included sixty patients with Behcet disease diagnoses, revealed that males were more likely than females to have the condition. The study found that all patients with neuro-Behcet had SNHL, the median age was 33 years, the prevalence of SNHL was 60%, the proportion of hearing loss in males was considerably higher than in females, the auditory presentation and severity of SNHL varied among individuals, and the severity increased with age. \u0026nbsp;Auditory manifestations and HB level are independent factors for SNHL, no relation between disease manifestation, disease duration, disease activity, disease treatment and severity of SNHL, no relation between level of platelets, TLC, CRP, ESR and severity of SNHL and no relation between level of platelets, HB, TLC, CRP, ESR and severity of SNHL.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval:\u0026nbsp;\u003c/strong\u003eResearch protocol was approved by the XXX Research Ethics Committee, the approval number: (MS-258-2023).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate: Informed consents were taken from all participants in this research.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u003c/strong\u003e Not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material: Available upon request.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests: No competing interests.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e Not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u0026nbsp;\u003c/strong\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number: Not applicable.\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eHirohata S, Kikuchi H. (2003): Beh\u0026ccedil;et\u0026rsquo;s disease. Arthritis Res Ther; 5 (3):139-4.\u003c/li\u003e\n\u003cli\u003eAhmet Karadağ , Mujde Karadağ , Adem Bora , Emrullah Hayta , A.Bahadır \u0026Ccedil;etin , Sevil C. Doğan , Kasım Durmuş \u0026amp; E. Elif Altuntaş. (2019): evaluation of hearing loss and tinnitus in behcet\u0026rsquo;s disease, European Archives of Oto-Rhino-Laryngology volume 276, pages2691\u0026ndash;2696.\u003c/li\u003e\n\u003cli\u003eInternational Study Group for Beh\u0026ccedil;et\u0026rsquo;s Disease. (1990): Criteria for diagnosis of Beh\u0026ccedil;et\u0026rsquo;s disease. Lancet; 335 (8697):1078-80.\u003c/li\u003e\n\u003cli\u003eMancini P, Atturo F, Di Mario A, Portanova G, Ralli M, De Virgilio A, et al. (2018): Hearing loss in autoimmune disorders: prevalence and therapeutic options. Autoimmun Rev; 17 (7):644\u0026ndash;52.\u003c/li\u003e\n\u003cli\u003eSota J, Vitale A, Orlando I, Lopalco G, Franceschini R, Fabiani C, et al. (2017): Auditory involvement in Behcet\u0026rsquo;s disease: relationship with demographic, clinical, and therapeutic characteristics. Clin Rheumatol.; 36 (2):445\u0026ndash;9.\u003c/li\u003e\n\u003cli\u003eSonbay ND, Saka C, Tatlican S, Vuralkan E, Aygener N, Eren C, et al. (2014): Audiological evaluation in patients with Behcet\u0026rsquo;s disease. J Laryngol Otol.; 128(8):694\u0026ndash;7.\u003c/li\u003e\n\u003cli\u003eDagli M, Eryilmaz A, Tanrikulu S, Aydın A, Gonul M, Gul U, et al. (2008): Evaluation of cochlear involvement by distortion product otoacoustic emission in Beh\u0026ccedil;et\u0026rsquo;s disease. Auris Nasus Larynx; 35: 333.\u003c/li\u003e\n\u003cli\u003eJoseph, F.G. \u0026amp; N.J. Scolding. (2007): Neuro-Beh\u0026ccedil;et\u0026apos;s disease in Caucasians: a study of 22 patients. Eur. J. Neurol. 14: 174\u0026ndash;180.\u003c/li\u003e\n\u003cli\u003eAkman-Demir, G. \u003cem\u003eet al. (\u003c/em\u003e2003): Cranial MRI in Beh\u0026ccedil;et\u0026apos;s disease: 134 examinations of 98 patients. Neuroradiology 45: 851\u0026ndash;859.\u003c/li\u003e\n\u003cli\u003eBhakta, B. B., Brennan1, P., James2, T. E., Chamberlain, M. A., Noble3, B. A., \u0026amp; Silman1, A. J. (1999): Beh\u0026ccedil;et\u0026rsquo;s disease: evaluation of a new instrument to measure clinical activity. In Rheumatology (Oxford), 38(8):728-33.\u003c/li\u003e\n\u003cli\u003eSoliman S. (1976): Speech discrimination audiometry using Arabic phonetically balanced words. Ain Shams Medical Journal, 27: 27\u0026ndash;30.\u003c/li\u003e\n\u003cli\u003eNewman CW, Sandridge SA, Jacobson GP. (1998): Psychometric adequacy of the Tinnitus Handicap Inventory (THI) for evaluating treatment outcome. J Am Acad Audiol. 1998 Apr;9(2):153-60. PMID: 9564679.\u003c/li\u003e\n\u003cli\u003eAlpsoy, E., Leccese, P., \u0026amp; Ergun, T. (2021). Editorial: Beh\u0026ccedil;et\u0026rsquo;s Disease: Epidemiology, Etiopathogenesis, Diagnosis and Treatment. In Frontiers in Medicine, 8:794874.\u003c/li\u003e\n\u003cli\u003eAlpsoy, E., Donmez, L., Onder, M., Gunasti, S., Usta, A., Karincaoglu, Y., Kandi, B., Buyukkara, S., Keseroglu, O., Uzun, S., Tursen, U., Seyhan, M., \u0026amp; Akman, A. (2007). Clinical features and natural course of Beh\u0026ccedil;et\u0026rsquo;s disease in 661 cases: A multicentre study. British Journal of Dermatology, 157(5), 901\u0026ndash;906.\u003c/li\u003e\n\u003cli\u003eAzizlerli, G., K\u0026ouml;se, A. A., Sarica, R., G\u0026uuml;l, A., Tutkun, I. T., Kula\u0026ccedil;, M., Tun\u0026ccedil;, R., Urgancioǧlu, M., \u0026amp; Diş\u0026ccedil;i, R. (2003). Prevalence of Beh\u0026ccedil;et\u0026rsquo;s disease in Istanbul, Turkey. International Journal of Dermatology, 42(10), 803\u0026ndash;806.\u003c/li\u003e\n\u003cli\u003eTursen, U., Gurler, A., \u0026amp; Boyvat, A. (2003). Evaluation of clinical findings according to sex in 2313 Turkish patients with Beh\u0026ccedil;et\u0026rsquo;s disease. International Journal of Dermatology, 42(5), 346\u0026ndash;351.\u003c/li\u003e\n\u003cli\u003eHouman MH, Neffati H, Braham A, Harzallah O, Khanfir M, Miled M, Hamzaoui K. (2007). Beh\u0026ccedil;et\u0026apos;s disease in Tunisia. Demographic, clinical and genetic aspects in 260 patients. Clin Exp Rheumatol, 4 (45):58-64.\u003c/li\u003e\n\u003cli\u003eEl Menyawi, M. M., Raslan, H. M., \u0026amp; Edrees, A. (2009). Clinical features of Behcet\u0026rsquo;s disease in Egypt. Rheumatology International, 29(6), 641\u0026ndash;646.\u003c/li\u003e\n\u003cli\u003eGemignani, G., Berrettini, S., Bruschini, P., Sellari-Franceschini, S., Fusari, P., Piragine, F., \u0026amp; Pasero, G. (1991). Hearing and vestibular disturbances in Beh\u0026ccedil;et\u0026apos;s syndrome. Ann Otol Rhinol Laryngol, 100(6):459-63.\u003c/li\u003e\n\u003cli\u003eAbdel Baki, N. M., Zahran, A. M. A., Dabbous, A. O., Koura, R. A., \u0026amp; Hamdy, M. M. (2021). Cervical vestibular evoked myogenic potential and high-frequency audiometry results in Beh\u0026ccedil;et\u0026rsquo;s disease. Egyptian Rheumatology and Rehabilitation, 48(3), 1-9.\u003c/li\u003e\n\u003cli\u003eCinar, S., Cinar, F., \u0026amp; Kiran, S. (2012). Is there a need for audiologic evaluation in patients with Beh\u0026ccedil;et disease? Ear Nose Throat J. 91(3):15-19.\u003c/li\u003e\n\u003cli\u003eMahdi, B., Mehdi, G. M., Reza, H. M., Mahdieh, T., \u0026amp; Taghi, S. M. (2007a). Hearing loss in Beh\u0026ccedil;et syndrome. Otolaryngology - Head and Neck Surgery, 137(3), 439\u0026ndash;442. \u003c/li\u003e\n\u003cli\u003eMahdi, B., Mehdi, G. M., Reza, H. M., Mahdieh, T., \u0026amp; Taghi, S. M. (2007b). Hearing loss in Beh\u0026ccedil;et syndrome. Otolaryngology - Head and Neck Surgery, 137(3), 439\u0026ndash;442.\u003c/li\u003e\n\u003cli\u003eKaradağ, A., Karadağ, M., Bora, A., Hayta, E., \u0026Ccedil;etin, A. B., Doğan, S. C., Durmuş, K., \u0026amp; Altuntaş, E. E. (2019). Evaluation of hearing loss and tinnitus in Behcet\u0026rsquo;s disease. European Archives of Oto-Rhino-Laryngology, 276(10), 2691\u0026ndash;2696.\u003c/li\u003e\n\u003cli\u003eKemal O, Anadolu Y, Boyvat A, Tatarağası A. (2013). Beh\u0026ccedil;et disease as a cause of hearing loss: A prospective, placebo-controlled study of 29 patients. Ear Nose Throat J. 92(3):112-120.\u003c/li\u003e\n\u003cli\u003eElidan J, Levi H, Cohen E, BenEzra D. (1991). Effect of cyclosporine A on the hearing loss in Beh\u0026ccedil;et\u0026rsquo;s disease. Annals of Otology, Rhinology \u0026amp; Laryngology, 100(6):464-468.\u003c/li\u003e\n\u003cli\u003eSoylu L, Aydoğan B, Soylu M, Ozsahinoğlu C. (1995). Hearing loss in Beh\u0026ccedil;et\u0026rsquo;s disease. Annals of Otology, Rhinology \u0026amp; Laryngology, 104(11):864-867.\u003c/li\u003e\n\u003c/ol\u003e "},{"header":"Tables","content":"\u003cp\u003eTables 1 to 9 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"egyptian-rheumatology-and-rehabilitation","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"43166","submissionUrl":"https://submission.springernature.com/new-submission/43166/3","title":"Egyptian Rheumatology and Rehabilitation","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Behcet disease, sensorineural hearing loss, Behcet disease current activity form","lastPublishedDoi":"10.21203/rs.3.rs-5509871/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5509871/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Behcet disease is a relapsing, chronic, systemic inflammatory illness characterized by mucocutaneous, articular, neurological, urogenital, vascular, intestinal, and pulmonary symptoms in addition to recurrent aphthous stomatitis, genital ulcerations, and ophthalmic disease. Objectives: Assessing effect of disease symptomatology, drugs used on sensorineural hearing loss severity.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e In this study, sixty adult Behcet disease patients participated. All underwent a comprehensive medical history, a basic audiological assessment, a Behcet disease current activity form, and a tinnitus handicap inventory scale.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e 60% of the participants, had sensorineural hearing loss; over half (55.6%) had mild sensorineural hearing loss, there is no statistically significant correlation between the \u0026nbsp;duration, the Behcet disease current activity form score, the tinnitus handicap inventory scale, vascular symptoms, and sensorineural hearing loss.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eprevalence of sensorineural hearing loss is 60%. Auditory manifestations and HB level are independent factors for SNHL, no relation between disease manifestation, \u0026nbsp;duration, disease activity, drugs \u0026nbsp;and severity of hearing loss, no relation between level of platelets, HB, \u0026nbsp;TLC, CRP, ESR and severity of hearing loss.\u003c/p\u003e","manuscriptTitle":"Behcet disease: Do individual symptomatology or certain drug intake reflect the severity of sensory neural hearing loss?","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-27 08:15:30","doi":"10.21203/rs.3.rs-5509871/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"66389806688315882518634143475430634886","date":"2025-03-26T15:32:30+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-03-26T10:22:04+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-03-26T02:52:40+00:00","index":"","fulltext":""},{"type":"submitted","content":"Egyptian Rheumatology and Rehabilitation","date":"2025-03-23T07:33:29+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"egyptian-rheumatology-and-rehabilitation","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"43166","submissionUrl":"https://submission.springernature.com/new-submission/43166/3","title":"Egyptian Rheumatology and Rehabilitation","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"279061a0-5287-4f42-88da-03e24afbbd66","owner":[],"postedDate":"March 27th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-04-04T06:38:46+00:00","versionOfRecord":[],"versionCreatedAt":"2025-03-27 08:15:30","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5509871","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5509871","identity":"rs-5509871","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}