Audiological Manifestations in VITILIGO – A Novel Study

ABSTRACT

Background and Objectives: Vitiligo is a common acquired localised depigmentation disorder resulting from progressive loss of melanocytes. Melanocytes in the skin, the uveal tract, and the ear are similar in their physiology and morphology and share a common embryological origin. The association between cutaneous depigmentation and ocular and auditory dysfunction is well known. This study aimed to evaluate the various audiological features in patients presenting with vitiligo.

Materials and Methods: A case-control study was conducted that included all patients presenting with vitiligo. Following the BSA and VASI assessments, both groups underwent tuning-fork tests and pure-tone audiometry. Goodman's classification of hearing loss (HL) was used to classify the severity.

Results: The mean age at presentation was 27.33 years, the mean age of onset was 24.57 years, and the duration was 1–3 years, with a male preponderance. 36.67% of the patients had a positive family history of vitiligo. The majority of patients had 1–5% body surface area involvement, with a mean VASI of 3 at presentation. 13.33% of patients had mild HL (26–40 dB) and 40% had minimal HL (16–25 dB) in the right ear. 46.67% of patients had minimal HL (16–25 dB) in the left ear.

Conclusion: All patients with vitiligo should undergo a comprehensive, routine audiological assessment to detect subclinical abnormalities early and prevent the impending complications of sensorineural hearing loss.

Key words: vitiligo, hearing loss, otologic manifestations, SNHL, mixed hearing loss.

INTRODUCTION:

Vitiligo is an acquired pigmentary disorder affecting 0.5%–2.0% of the population.

Worldwide, it can be seen at any age [1] and in both sexes, with a similar incidence [2]. Vitiligo can be associated with many comorbidities[3]. The exact aetiology of vitiligo is unknown. However, genetic, neural, immunological and self-destructive pathomechanisms are said to be involved. Autoantibodies directed against melanocyte antigens lead to the destruction of melanocytes [4].

In the cochlea, melanocytes are most conspicuous in the stria vascularis, in which they form the intermediate cell layer, but are also present in other parts and tissues of the cochlea.

Melanocytes are required for the maintenance of normal function of the stria vascularis and cochlea, for the development of endocochlear potentials, and for the ion and fluid gradient between the endolymph and the perilymph, all of which are critical for hair-cell survival[5].

The otic melanocytes are located in the stria vascularis, hair cells, endolymphatic sac, and vestibular organ[6]. In the stria vascularis, otic melanocytes modulate the function of Na+/K+-ATPase and potassium channels, which are essential for creating endocochlear electrical potential[7].

The theory to explain the pathogenesis of auditory findings in vitiligo is that an autoimmune mechanism may destroy melanocytes. The presence of various immunologic abnormalities in patients with vitiligo supports this hypothesis. Pigment cells are widely distributed in the body, and the inner ear contains a substantial number of melanocytes[8].

Vitiligo is a multifactorial disorder related to both genetic and non-genetic factors. However, the exact aetiology of vitiligo is unknown. Vitiligo is one of the few autoimmune diseases in which environmental factors are well recognised.

A positive family history is seen in 7%–36% of cases. Around 20% of these cases have at least one affected first-degree relative, suggesting a role for genetic factors in the pathogenesis. A positive association between vitiligo and HLA-DR4 has also been reported. Other HLA associations linked to vitiligo include HLA-DR1, DR7, A2, B13, B21, and Cw6.

An important theory of vitiligo pathogenesis is the oxidative stress theory. This theory suggests intraepidermal accumulation of reactive oxygen species (ROS), the most notorious of which is H2O2.

Patients can present with vitiliginous patches over the pinna. Sensorineural hearing loss has been reported in 4–37% of patients with vitiligo. In most of these studies, patients were asymptomatic but on audiological evaluation were diagnosed with hearing loss[9,10,11]. Patients may experience significant hearing loss, especially at high and extended high frequencies. Conductive hearing loss was reported in two studies involving patients with vitiligo [12,13]. Conductive loss in vitiligo is unlikely, as melanocytes do not participate in the conductive mechanism of hearing because they are only present in the inner ear. Conductive hearing loss can only be seen in vitiligo if there is any coexisting middle ear pathology[6].

This is a hospital-based case-control study aimed at examining various audiological features in patients presenting with vitiligo.

MATERIALS AND METHODS:

This study was conducted in the Department of Otorhinolaryngology at Dr. B. R. Ambedkar Medical College and Hospital, Bengaluru. A total of 30 cases of vitiligo and 30 age- and sex-matched controls, attending the outpatient and inpatient wards of the Department of ENT and Dermatology and consenting to the study between October 2020 and October 2021, were included and evaluated in this study. Patients who were unwilling to participate, those with pre-existing audiological abnormalities, and those with other causes of depigmentary disorders were excluded from the study.

Complete otological and audiological examinations of both ears were performed for all patients and the control group. Goodman's classification of hearing loss was used to classify the severity of hearing deficit.

Data were analysed using SPSS 22. The chi-square test was used to assess significance for qualitative data. Continuous data were reported as mean ± standard deviation. An independent t-test was used to test for significance and determine the mean difference between two quantitative variables and two qualitative variables, respectively.

A p-value of <0.05 was considered statistically significant after meeting all assumptions of statistical tests.

Figure 1: Focal vitiligo Figure 2: Vitiligo patches over right ear

RESULTS:

The mean age among cases and controls was 27.33 years, the mean age at onset of vitiligo lesions was 24.57 years, with a mean duration of 2.87 years, a mean BSA of 7.00%, and a mean VASI of 5.31.

Family history of vitiligo was found in 11 patients (36.67%), and 19 (63.3%) had a negative family history.

Among vitiligo patients, 25 patients (83.33%) were free from comorbidities, 1 (3.33%) had a history of hypertension, and 2 (6.67%) each had a history of type 2 DM and hypothyroidism, respectively and were on regular treatment. In the control group, no one had a history of comorbidities.

Table 1: Lesions Over Ears Distribution between the two groups

x²=9.231, df=1, p=0.002

Table 2: Rinne distribution between two groups

Right: x²=1.017, df=1, p=0.313

Left: x²=1.017, df=1, p=0.313

Table 3: Weber Distribution between two groups.

Right: x²=1.071, df=1, p=0.301

Left: x²=1.017, df=1, p=0.313

Table 4: Absolute Bone Conduction Distribution between the two groups

Right: x²=1.071, df=1, p=0.301

Left: x²=0, df=1, p=1.000

Table 5: Pure Tone Audiometry Distribution between two groups

Right: x²=11.6, df=2, p=0.003

Left: x²=9.932, df=1, p=0.002

Table 6: Association between vitiligo lesions over the ears and findings on tuning-fork tests and PTA.

Table 7: Association between VASI and PTA findings on the right and left sides

Table 8: Association between BSA and PTA findings on the right and left sides

DISCUSSION:

Vitiligo is an acquired depigmentary disorder that destroys melanocytes in the skin, hair bulbs, mucous membranes, uveal tract, retinal pigment epithelium of the eyes, inner ear, and leptomeninges [14]. There is a paucity of literature on the various audiological abnormalities associated with vitiligo. Our study thus aims to contribute to this area.

In the present study, tuning fork tests, including Rinne’s test, Weber’s test, and the Absolute bone conduction test, were performed on all patients and controls. There was no significant difference in tuning-fork test results between the two groups in either ear.

However, in studies by KVT Gopal et al. [15], Pathak GK et al. [4], Dabbous et al. [4] and Prabha N et al. [4], all three tuning-fork tests were performed on all vitiligo patients. In none of these studies were the tuning-fork test results mentioned. Thus, our study contributes to the literature on tuning-fork test findings in patients with vitiligo.

In the present study, SNHL was noted in the right ear of 16 patients with vitiligo (53.33%) (4 had mild and 12 had minimal SNHL) and in the left ear of 14 patients with vitiligo (46.67%). However, SNHL was observed in only 4 healthy controls (13.33%) in the right ear and in 3 (10%) in the left ear. Thus, we noted a significantly higher prevalence of hearing loss in vitiligo patients compared to healthy controls, consistent with another case-control study by Genedy R et al. [16], which examined 40 vitiligo patients and 20 healthy controls (HCs).

Our observation is consistent with another case-control study by Genedy R et al. [16], in which 40 patients with vitiligo and 20 healthy controls (HCs) were examined. Based on the mean PTA, none of the HCs had hearing loss, but hearing loss was detected in 12 ears from 7 patients (17.5%). Five patients had bilateral hearing loss, and two had unilateral hearing loss (right-sided only). There was a significantly higher prevalence of hearing loss among patients than among HCs [16].

In another case-control study by Tosti et al. [8], the prevalence of hearing loss was significantly higher among patients with vitiligo (8/50, 16%) than in healthy controls.

An interesting finding across all the above studies, including the present study, is that none of these patients reported clinically reduced hearing. In most studies, SNHL is reported in patients with vitiligo. Conductive hearing loss is unlikely in patients with vitiligo, as melanocytes play no role in the conductive mechanism of hearing and are absent from the inner ear. Conductive hearing loss can be noted in vitiligo patients only when there is an associated middle ear pathology [4].

CONCLUSION:

A significantly higher prevalence of sensorineural hearing loss was noted in both ears among vitiligo patients in comparison to controls without vitiligo. An interesting finding in our study is that none of the vitiligo patients with audiological findings complained of clinical difficulty in hearing. Thus, a thorough audiological assessment is routinely recommended for all vitiligo patients to detect subclinical abnormalities, such as sensorineural hearing loss, early. These patients should also be informed about the associated risks of exposure to loud noise and ototoxic drugs, which are detrimental to hearing.

References:

1. Yaghoobi R, Omidian M, Bagherani N. Vitiligo: a review of the published work. J Dermatol 2011;38:419–31.

2. Karadag R, Esmer O, Karadag AS, Bilgili SG, Cakici O, Demircan YT, et al. Evaluation of ocular findings in patients with vitiligo. Int J Dermatol 2016;55:351–5

3. Elbuluk N, Ezzedine K. Quality of life, burden of disease, comorbidities and systemic effects in vitiligo patients. Dermatol Clin 2017;35:117–28.

4. Prabha N, Arora R, Chhabra N, Jati M, Nagarkar NM. Audiological Abnormalities in Vitiligo Patients: A Hospital-Based Cross-Sectional Study. Int Arch Otorhinolaryngol 2020;24(2):149–53.

5. Aydogan K, Turan OF, Onart S, Karadogan SK, Tunali S. Audiological abnormalities in patients with vitiligo. Clin Exp Dermatol 2006;31(1):110–3.

6. Maheshwari A, Panigrahi R, Mahajan S. Vitiligo associated hypoacusis: a case-control study. Int J Otorhinolaryngol Head Neck Surg 2016;2(02):77–81

7. Tachibana M. Cochlear melanocytes and MITF signaling. J Investig Dermatol Symp Proc 2001;6(01):95–8

8. Tosti A, Bardazzi F, Tosti G, Monti L. Audiologic abnormalities in cases of vitiligo. J Am Acad Dermatol 1987;17(2):230–3

9. Mahajan BB, Nagpal R. Repigmentation in vitiligo. In: Relhan V, Garg VK, Ghunawat, Mahajan K, editors. Comprehensive Textbook on Vitiligo. 1st ed. Boca Raton, FL: CRC Press; 2020. p. 63–66.

10. Majumder PP. Genetics and Prevalence of Vitiligo Vulgaris. In: Hann SK, Nordlund JJ, and Lerner AB, editors. Vitiligo: A Monograph on the Basic and Clinical Science. Oxford, UK: Blackwell Science Ltd.;2000. p. 18–20.

11. Passeron T, Ortonne JP. In: Vitiligo and Other disorders of Hypopigmentation. Bolognia JL, Schaffer JV, Cerroni L, editors. Bolognia Dermatology. 4th edition. Mosby; Elsevier, 2018, pp. 1087–96.

12. Geel NV, Speeckaert R. In: Acquired Pigmentary disorders. Griffiths C, Barker J, Blieker T, Chalmers R, Creamer D, editors. Rook’s Textbook of Dermatology. 9th edition. Oxford: Wiley-Blackwell Publishers: 2016, pp. 88.34–88.40.

13. Harris JE. Chemical-Induced Vitiligo. Dermatol Clin 2017;35(2):151–61.

14. Arora AK, Kumaran MS. Pathogenesis of vitiligo: An update. Pigment Int 2017;4:65–77.

15. Kumar R, Parsad D. Melanocytorrhagy and apoptosis in vitiligo: connecting jigsaw pieces. Indian J Dermatol Venereol Leprol 2012;78(1):19–23

16. Genedy R, Assal S, Gomaa A, Almakkawy B, Elariny A. Ocular and auditory abnormalities in patients with vitiligo: a case-control study. Clin Exp Dermatol 2021;46(6):1058–66.