Potential Autoimmune Association between Benign Paroxysmal Positional Vertigo and Immune-mediated Skin Conditions: Population-based Cohort Study

Background Benign paroxysmal positional vertigo (BPPV), an idiopathic disorder of sudden sensorineural hearing loss and vertigo, shares many similarities with two common skin conditions, atopic dermatitis (AD) and vitiligo. Recent studies have suggested that BPPV may be related to or triggered by autoimmune conditions, notably hypothyroidism and giant cell arteritis (GCA). Objective These evidences prompted the authors to entertain the possibility of immunological bridge between BPPV and the two skin conditions. The authors have tested this hypothesis with population-based cohort from the National Health Insurance Service Database of Korea. Methods A cohort of 1.1 million patients was extracted from the DB. Using χ2 tests, prevalence of the two skin disorders in terms of BPPV status was analysed. Results In AD patients, the prevalence of BPPV was 30% lower, while there was no statistically significant relationship between BPPV prevalence and vitiligo. The relationship between vitiligo and BPPV was significant in younger subgroup only. Socio-economic subgroup analysis revealed the observed patterns are primarily a middle-upper class phenomenon. Limitations Uncertainty regarding temporal sequence of onset, and lack of detail on disease severity and subtype might have kept the authors from drawing more refined conclusion. Conclusion AD and vitiligo might be linked to BPPV through the action of certain components of cellular immunity, but follow-up studies based on large population cohort would be needed to add more substance to our findings.


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Benign paroxysmal positional vertigo (BPPV), along with Ménière disease (MD) and labyrhinthitis, is one of 23 the most commonly encountered forms of vertiginous disorder. Accounting for almost 50% of all individuals with 24 peripheral vestibular dysfunction [1], one-year and lifetime prevalence of this largely idiopathic entity is believed 25 to be around 1.6% and 2.4% respectively, with a slight predilection for females [2,3,4]. The vertigo of sudden 26 onset, that is characteristic of BPPV, is thought to be instigated by displacement of inner ear crystals (otoliths),

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with the stones lodging within the lumen of the semi-circular canals [5], which in turn culminates in perturbed BPPV. Studies over the past several years have reinforced the notion of the endolymphatic sac, where these "ear 3 rocks" originate, as a vibrant hub of immunological interactions, rather than an inert structural locale [6]. The 4 labyrinthine sac is known to harbour inner ear autoantigens of various molecular weights, which can trigger type 5 II (surface antigens) or type III (antigen-antibody immunocomplexes) hypersensitivities [7,8]. One facet of the 6 autoimmune hypothesis points to this type of immune-complex formation and diffusion of these complexes into income brackets (deciles), and then regrouped as lower (brackets 1 through 4), middle (brackets 5 through 7), or 1 the extent of their disability. For the entire cohort, the "baseline" prevalence of BPPV, AD, and vitiligo were 2 computed at 0.69%, 0.72% and 0.11%, respectively.
3 Prevalence of BPPV in terms of skin disease status. The prevalence of BPPV in AD individuals was 0.72%.

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In non-AD patients, the prevalence was 0.50%. The finding was statistically significant (p=0.023). The prevalence 5 of BPPV in vitiligo and non-vitiligo individuals was 0.11% and 0.14%, respectively. However, these relationships 6 were not statistically significant (p=0.464).
7 Sex and age. A similar pattern prevailed after male and female cohorts were considered separately, although the 8 relationship between BPPV and AD was not statistically significant in males (p=0.119). Age group analysis 9 revealed that the higher prevalence of vitiligo in BPPV patients held true only for the younger individuals 10 (p=0.000). Other findings were not statistically significant.

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Socioeconomic subgroups. On χ 2 test, the BPPV-vitiligo relationship was valid only in the "middle" income 12 tier (brackets 5 through 7, p=0.000). On the other hand, the lower BPPV prevalence in AD patients was seen only 13 in the "upper" tier (brackets 8 through 10, p=0.037). Other relationships were not statistically significant.
14 Disability. The BPPV-AD/vitiligo relationship was also analysed by disability status. χ 2 analysis revealed

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The authors acknowledge that this study was subject to some limitations. Due to its cross-sectional nature, 20 temporal relations between BPPV and skin disorders could not be established. Also, lack of information regarding 21 disease severity and subtype (e.g., anterior or horizontal canal versus posterior canal BPPV [24,25]) had impeded 22 more detailed analysis, which would have allowed the authors to propose more elaborate disease mechanism.

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Finally, it was revealed by subgroup analysis that the relationship between the skin conditions and BPPV was 24 statistically significant only for individuals without disability.

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In conclusion, the present study represents a unique attempt to form a potential link between autoimmune 26 conditions and BPPV, which has been considered to originate from mechanical/physical causes for the most part.

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Despite a few shortcomings, the study allowed the authors to glimpse through the underlying patho-mechanism 28 of three puzzling conditions, and on the process gain some unique insights and perspectives. Further studies, with 29 more thorough and sophisticated databases, would enable us to build upon this ground and yield more refined