Clinical Rheumatology

, Volume 34, Issue 7, pp 1311–1316

Renal involvement in secondary amyloidosis of Muckle-Wells syndrome: marked improvement of renal function and reduction of proteinuria after therapy with human anti-interleukin-1β monoclonal antibody canakinumab

  • Roberto Scarpioni
  • Donato Rigante
  • Luca Cantarini
  • Marco Ricardi
  • Vittorio Albertazzi
  • Luigi Melfa
  • Antonio Lazzaro
Case Based Review

DOI: 10.1007/s10067-013-2481-2

Cite this article as:
Scarpioni, R., Rigante, D., Cantarini, L. et al. Clin Rheumatol (2015) 34: 1311. doi:10.1007/s10067-013-2481-2

Abstract

Muckle-Wells syndrome (MWS) is a rare hereditary autoinflammatory disorder characterized by recurrent urticaria-like skin rashes, arthralgias, conjunctivitis, hypoacusia, and risk of reactive AA amyloidosis due to the progressive accumulation of amyloid fibrils in different organs. Its genetic defect lies in mutations in the NLRP3 gene, encoding the cryopyrin protein, and resulting in interleukin (IL)-1β oversecretion. Renal involvement, in terms of proteinuria or renal insufficiency, can be observed in up to 25 % of patients. Herein, we describe our experience with two Caucasian patients, father and son, aged 52 and 26 years, respectively, heterozygous for both V198M and R260W NLRP3 mutations who had AA amyloid deposits on renal biopsy. The fully human monoclonal antibody canakinumab, providing selective and prolonged IL-1β blockade, was administered in both patients every 60 days over a period of 18 months. This treatment allowed to obtain amazing results: a rapid disappearance of any clinical symptoms, the stable normalization of serum amyloid-A and, furthermore, a marked improvement of glomerular filtration rate and proteinuria with no adverse events. Our data, though limited to only two patients, emphasize that therapeutic intervention with canakinumab, suppressing both inflammation and IL-1β-mediated manifestations, can contribute to improve kidney function in MWS with overt renal amyloidosis.

Keywords

AmyloidosisCanakinumabInterleukin-1Muckle-Wells syndrome

Copyright information

© Clinical Rheumatology 2014

Authors and Affiliations

  • Roberto Scarpioni
    • 1
  • Donato Rigante
    • 2
  • Luca Cantarini
    • 3
  • Marco Ricardi
    • 1
  • Vittorio Albertazzi
    • 1
  • Luigi Melfa
    • 1
  • Antonio Lazzaro
    • 4
  1. 1.Nephrology and Dialysis Unit, Department of Medicine“Guglielmo da Saliceto” Hospital AUSL PiacenzaPiacenzaItaly
  2. 2.Institute of Pediatrics, Università Cattolica Sacro CuoreRomeItaly
  3. 3.Research Center of Systemic Autoimmune and Autoinflammatory Diseases Rheumatology UnitPoliclinico “Le Scotte” University of SienaSienaItaly
  4. 4.Haematology Unit, Department of Oncohematology“Guglielmo da Saliceto” Hospital AUSL PiacenzaPiacenzaItaly