Spectrum of clinical features in Muckle-Wells syndrome and response to anakinra
Article first published online: 5 FEB 2004
Copyright © 2004 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 50, Issue 2, pages 607–612, February 2004
How to Cite
Hawkins, P. N., Lachmann, H. J., Aganna, E. and McDermott, M. F. (2004), Spectrum of clinical features in Muckle-Wells syndrome and response to anakinra. Arthritis & Rheumatism, 50: 607–612. doi: 10.1002/art.20033
- Issue published online: 5 FEB 2004
- Article first published online: 5 FEB 2004
- Manuscript Accepted: 21 OCT 2003
- Manuscript Received: 14 MAY 2003
- Medical Research Council
- NHS Research and Development funds
- Special Trustees of St. Bartholomew's
- Royal London Joint Research Board
Mutations in the NALP3/CIAS1/PYPAF1 gene are associated with the autoinflammatory diseases Muckle-Wells syndrome (MWS), familial cold autoinflammatory syndrome (FCAS), and neonatal-onset multisystem inflammatory disease (NOMID), which is also known as chronic infantile neurologic, cutaneous, articular (CINCA) syndrome. Molecular studies suggest that NALP3 is involved in the processing of interleukin-1β (IL-1β), prompting us to investigate whether IL-1 blockade may be therapeutic in patients with MWS.
We reviewed the clinical features of 3 members of a family, all of whom had MWS associated with the NALP3 variant V200M (also designated V198M), and evaluated the response of their inflammatory disease to treatment with the recombinant human IL-1 receptor antagonist anakinra. The subjects kept a diary of symptoms and underwent fortnightly clinical and laboratory assessments, including measurement of the serum amyloid A protein concentration.
Each subject had fever, rashes, arthralgia, conjunctivitis, sensorineural deafness, and an intense acute-phase response characteristic of MWS. However, additional features were identified, including exacerbation of their disease by cold and neurologic manifestations, that have hitherto been described only in FCAS and NOMID, respectively. Clinical and serologic evidence of active inflammatory disease resolved rapidly and completely during treatment with anakinra.
The remarkable response of MWS to anakinra suggests that IL-1β has a fundamental role in the pathogenesis of inflammation associated with mutations in the NALP3 gene, and supports study of IL-1 inhibition in patients with NOMID/CINCA syndrome or FCAS. The clinical features of the various syndromes associated with mutations in the NALP3 gene may overlap to a greater extent than has previously been recognized.