Cryopyrin-associated periodic syndromes: otolaryngologic and audiologic manifestations

Otolaryngol Head Neck Surg. 2011 Aug;145(2):295-302. doi: 10.1177/0194599811402296.


Objective: Cryopyrin-associated periodic syndromes (CAPS) represent a spectrum of CIAS1 gene-mediated autoinflammatory diseases characterized by recurrent systemic inflammation. The clinical spectrum of CAPS varies from mild to severe and includes the syndromes historically described as familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease (NOMID). This article presents the largest cohort of patients with CAPS. The objective is to describe the pathogenesis, otolaryngologic, and audiologic manifestations of CAPS.

Study design: Prospective (2003-2009).

Setting: National Institutes of Health.

Subjects and methods: Fifty-seven patients with a diagnosis of CAPS were identified (31 NOMID, 11 NOMID/MWS, 9 MWS, and 6 FCAS). Comprehensive data regarding clinical manifestations, audiologic phenotype, and fluid attenuation inversion recovery MRI (FLAIR-MRI) of the brain and inner ear were obtained.

Results: Complete audiologic data obtained on 70% of ears revealed conductive hearing loss in 4 (11%) NOMID ears and mixed hearing loss in 5 (13%) NOMID and 2 (14%) NOMID/MWS ears. Sensorineural hearing loss (SNHL), worse in higher frequencies, was the most common type of hearing loss and was present in 23 (61%) NOMID, 10 (71%) NOMID/MWS, and 4 (33%) MWS ears. All of the patients with FCAS had normal hearing except 2, who had SNHL from 4 to 8 kHz. On FLAIR-MRI sequence, cochlear enhancement was noted in 26 of 29 (90%) NOMID, 6 of 11 (55%) NOMID/MWS, 3 of 9 (33%) MWS, and 1 of 6 (17%) FCAS patients and was significantly associated with the presence of hearing loss. Maxillary sinus hypoplasia and mucosal thickening were found in 39% and 86% of the cohort, respectively.

Conclusion: CIAS1 pathway–mediated CAPS is associated with unregulated autoinflammation mediated by interleukin-1 in the cochlea and hearing loss. Timely diagnosis is crucial to initiate early treatment with interleukin-1 receptor antagonists.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Audiometry, Pure-Tone
  • Bone Conduction
  • Child
  • Child, Preschool
  • Cochlea / metabolism
  • Cryopyrin-Associated Periodic Syndromes / complications*
  • Cryopyrin-Associated Periodic Syndromes / diagnosis
  • Cryopyrin-Associated Periodic Syndromes / physiopathology
  • Female
  • Follow-Up Studies
  • Hearing / physiology*
  • Hearing Loss, Mixed Conductive-Sensorineural / diagnosis
  • Hearing Loss, Mixed Conductive-Sensorineural / etiology*
  • Hearing Loss, Mixed Conductive-Sensorineural / physiopathology
  • Hearing Loss, Sensorineural / diagnosis
  • Hearing Loss, Sensorineural / etiology*
  • Hearing Loss, Sensorineural / physiopathology
  • Humans
  • Hyperplasia
  • Infant
  • Interleukin-1 / biosynthesis
  • Magnetic Resonance Imaging
  • Male
  • Maxillary Sinus / pathology*
  • Middle Aged
  • Paranasal Sinus Diseases / etiology*
  • Paranasal Sinus Diseases / pathology
  • Prognosis
  • Prospective Studies
  • Respiratory Mucosa / pathology
  • Young Adult


  • Interleukin-1