Abstract
BackgroundMuckle-Wells-syndrome (MWS) is an autoinflammatory disease characterized by systemic and organ-specific inflammation due to excessive interleukin (IL)-1 release. Inner ear inflammation results in irreversible sensorineural hearing loss, if untreated. Early recognition and therapy may prevent deafness. The aims of the study were to characterize the spectrum of hearing loss, optimize the otologic assessment for early disease and determine responsiveness to anti-IL-1-therapy regarding hearing.MethodsA single center prospective cohort study of children and adults with MWS was performed. Standardized clinical, laboratory and otologic assessments including standard pure tone audiometry, additional high tone thresholds, vestibular organ testing, tinnitus evaluation and functional disability classes were determined serially. Pure-tone-average models were developed and evaluated. Risk factors for hearing loss and the impact of anti-IL-1 treatment were determined.ResultsA total of 23 patients with genetically confirmed MWS were included, of whom 63 % were females; 52 % were children. At baseline all patients had active MWS; 91 % reported clinically impaired hearing with 74 % having an abnormal standard assessment (0.5–4 kHz). In contrast, high frequency pure tone averages (HF-PTA) were abnormal in all symptomatic patients including those with early hearing loss (sensitivity 100 %). Females were at highest risk for hearing loss even after adjustment for age (p = 0.008). Treatment with IL-1 blockade resulted in improved or stable hearing in 91 % of patients.ConclusionsEarly inner ear inflammation in MWS primarily affects the high frequencies, beyond the range of standard otologic assessment tools. The HF-PTA is a sensitive tool to detect imminent hearing loss and monitor treatment response.Electronic supplementary materialThe online version of this article (doi:10.1186/s12969-015-0041-9) contains supplementary material, which is available to authorized users.
Highlights
Muckle-Wells-syndrome (MWS) is an autoinflammatory disease characterized by systemic and organspecific inflammation due to excessive interleukin (IL)-1 release
Reports suggest the reversibility of early inner ear inflammation and improved hearing with IL-1 blockade in MWS patients [11, 16,17,18,19,20]
The aims of the study were 1) to characterize the distinct pattern of hearing loss at diagnosis of MWS, 2) to modify the established standard 4 pure tone average (4PTA) assessment tool to the hearing loss characteristics of MWS patients and assess its sensitivity in detecting hearing loss and 3) to determine risk factors associated with hearing loss in MWS and the effects of IL-1-inhibition
Summary
Muckle-Wells-syndrome (MWS) is an autoinflammatory disease characterized by systemic and organspecific inflammation due to excessive interleukin (IL)-1 release. Inner ear inflammation results in irreversible sensorineural hearing loss, if untreated. The aims of the study were to characterize the spectrum of hearing loss, optimize the otologic assessment for early disease and determine responsiveness to anti-IL-1-therapy regarding hearing. Muckle-Wells syndrome (MWS) is an autosomal dominant autoinflammatory disease in the clinical spectrum of cryopyrin-associated periodic syndrome (CAPS). Inner ear inflammation and hearing loss may initially not impact communication in quiet. Reports suggest the reversibility of early inner ear inflammation and improved hearing with IL-1 blockade in MWS patients [11, 16,17,18,19,20]. MWS treatment options include anakinra [17], a short acting IL-1 receptor antagonist and canakinumab, a fully human monoclonal antibody providing selective and prolonged IL-1β blockade [21] and rilonacept, an IL-1 trap fusion protein [16]
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