Sensorineural hearing loss associated with autoinflammatory diseases—Otological manifestations of DFNA34 and efficacy of the interleukin 1 receptor antagonist

<p>Autoinflammatory diseases are characterized by hyperactivation of the innate immune system without high titers of autoantibodies or antigen-specific T cells. Cryopyrin-associated periodic syndrome (CAPS) is a spectrum of inherited autoinflammatory syndromes caused by a gain-of-function mutation of the NLRP3 gene. CAPS includes familial cold autoinflammatory syndrome, Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease (NOMID). Among these, MWS and NOMID are associated with a high incidence of sensorineural hearing loss. Recently, we identified a missense mutation, p.Arg918Gln in NLRP3 in a family segregating sensorineural hearing loss without any other target-organ manifestations of CAPS. The family members carrying the mutation had bilateral sensorineural hearing loss with onset in the late 2^nd to 4^th decade of life. The hearing loss initially primarily affected high frequencies and slowly progressed. We also identified another unrelated family segregating p.Arg918Gln mutation. In the family, hearing loss was accompanied by autoinflammatory signs and symptoms. Postcontrast magnetic resonance imaging with fluid-attenuation inversion recovery showed pathologic enhancement of the cochlea in the affected members. The hearing loss was reversed or improved by IL-1β blockade therapy. These observations suggest that mutations of NLRP3 may cause hearing loss due to local autoinflammation within the inner ear.</p>