title: Early detection of sensorineural hearing loss in Muckle-Wells-syndrome.
abstract: BACKGROUND
  Muckle-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.
  
  
  METHODS
  A 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.
  
  
  RESULTS
  A 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.
  
  
  CONCLUSIONS
  Early 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.
authors.affiliation: Department of Pediatrics, Division of Pediatric Rheumatology, University Hospital Tuebingen, Hoppe-Seyler-Str. 1, D-72076, Tuebingen, Germany. kuemmerle.deschner@uni-tuebingen.de.
authors.forename: Jasmin B
authors.initials: JB
authors.lastname: Kuemmerle-Deschner
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Klinikum Stuttgart, Stuttgart, Germany. a.koitschev@klinikum-stuttgart.de.
authors.forename: Assen
authors.initials: A
authors.lastname: Koitschev
authors.affiliation: Department of Medical Imaging, University of Toronto, Toronto, Canada. pascal.tyrrell@utoronto.ca.
authors.forename: Pascal N
authors.initials: PN
authors.lastname: Tyrrell
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Halle (Saale), Halle (Saale), Germany. stefan.plontke@uk-halle.de.
authors.forename: Stefan K
authors.initials: SK
authors.lastname: Plontke
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, University Hospital Tuebingen, Tuebingen, Germany. norbert.deschner@uni-tuebingen.de.
authors.forename: Norbert
authors.initials: N
authors.lastname: Deschner
authors.affiliation: Department of Pediatrics, Division of Pediatric Rheumatology, University Hospital Tuebingen, Hoppe-Seyler-Str. 1, D-72076, Tuebingen, Germany. sandra.hansmann@med.uni-tuebingen.de.
authors.forename: Sandra
authors.initials: S
authors.lastname: Hansmann
authors.affiliation: Department of Pediatrics, Division of Pediatric Rheumatology, University Hospital Tuebingen, Hoppe-Seyler-Str. 1, D-72076, Tuebingen, Germany. katharina.ummenhofer@googlemail.com.
authors.forename: Katharina
authors.initials: K
authors.lastname: Ummenhofer
authors.affiliation: CeGaT, Center for Genomics and Transcriptomics, Tuebingen, Germany. peter.lohse@cegat.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Lohse
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Klinikum Stuttgart, Stuttgart, Germany. ch_haferkamp@yahoo.de.
authors.forename: Christiane
authors.initials: C
authors.lastname: Koitschev
authors.affiliation: Department of Pediatrics, Division of Pediatric Rheumatology, University Hospital Tuebingen, Hoppe-Seyler-Str. 1, D-72076, Tuebingen, Germany. susa.benseler@gmail.com.|Rheumatology, Department of Pediatrics, Alberta Children's Hospital, University of Calgary, Calgary, Canada. susa.benseler@gmail.com.
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Benseler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001301:Audiometry, Pure-Tone / Q000379:methods; D001309:Auditory Threshold; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D056587:Cryopyrin-Associated Periodic Syndromes / Q000150:complications* / Q000235:genetics; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy*; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use*; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D011446:Prospective Studies; D012307:Risk Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D002352:Carrier Proteins; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; C541220:canakinumab