Hearing improvement in a variant Muckle–Wells syndrome case in response to IL-1 receptor antagonism

Background

The proinflammatory cytokine IL-1β has been implicated in the pathogenesis of a number of the hereditary periodic fever syndromes. One such syndrome, Muckle–Wells syndrome (MWS), is characterised by the triad of urticaria, progressive sensorineural deafness and systemic amyloid A amyloidosis. Other features include rigors, leucocytosis, raised acute phase reactants and serum amyloid A levels. A number of case reports have recently emerged involving treatment with the recombinant human IL-1 receptor antagonist, Anakinra (Kineret; Amgen, Cambridge, UK) [1–3].

Case report

A 59-year-old caucasian female presented with increasingly severe and intractable disease over a 15-year period. In addition to the above features, she also exhibited papilloedema and chronic aseptic meningitis. No other family members were affected. Upon commencing treatment with Anakinra, there was complete resolution of her inflammatory symptoms within 24–48 hours, and rapid normalisation of her C-reactive protein and serum amyloid A levels (from 415.0 mg/l to 12.6 mg/l after 4 weeks of therapy). Her intracranial pressure and CSF white cell counts also returned to normal. Audiometry confirmed a 15–30 decibel improvement in the 250–4000 Hz frequency range in each ear. No mutations of the responsible gene – NALP3/CIAS1 on chromosome 1q44 – were demonstrated on her DNA sequencing.

Discussion

Our patient is the oldest reported sporadic case of MWS. Heterozygous missense mutations have thus far been reported in only 60% of MWS patients analysed [4]. The confirmed improvements in hearing, intracranial pressure, and CSF white cell counts seen here with Anakinra lend further support to the treatment of the autoinflammatory conditions by targeting IL-1. The pathogenesis of the sensorineural deafness in MWS is unclear although it is postulated that expression of mutated NALP3/CIAS1 in cartilage may have a causative role [3].