 |
|
Phenotype, Genotype, and Sustained Response to Anakinra in 22 Patients With Autoinflammatory Disease Associated With CIAS-1/NALP3 Mutations
Kieron S. Leslie, MRCP, DTN&H;
Helen J. Lachmann, MD, MRCP;
Elizabeth Bruning, BSC, LLB;
John A. McGrath, MD, FRCP;
Alison Bybee, PhD;
J. Ruth Gallimore, BSC;
Philip F. Roberts, FRCP, FRCPath;
Patricia Woo, PhD, FRCP, FRCPCH;
Clive E. Grattan, MD, FRCP;
Philip N. Hawkins, PhD, FRCP
Arch Dermatol. 2006;142:1591-1597.
Objective To characterize the multisystem chronic inflammatory phenotype, dermatopathologic features, and response to therapy with interleukin 1 receptor antagonist (anakinra) in patients with mutations in the CIAS-1/NALP3 gene.
Design Retrospective review of medical records and evaluation of histologic findings.
Setting The National Amyloidosis Centre, London, and a tertiary referral clinic for urticaria.
Patients Twenty-two individuals from 13 families with autoinflammatory disease associated with CIAS-1/NALP3 mutations.
Main Outcome Measures Phenotype, genotype, skin histologic findings, and response to treatment with anakinra.
Results Five heterozygous missense mutations were identified in CIAS-1/NALP3. Skin histologic findings revealed marked vascular dilatation and neutrophilic infiltration involving small vessels and eccrine glands. Serologic evidence of intense inflammation was present in untreated patients, with median serum amyloid A protein and C-reactive protein levels of 141 and 38 mg/L, respectively. Fifteen patients received anakinra for up to 39 months, all of whom achieved serologic remission and complete resolution of fever, rash, conjunctivitis, and rheumatic symptoms, without any adverse effects. Six patients had AA (reactive systemic) amyloidosis, 2 of whom died of renal failure complications before interleukin 1–inhibiting therapy was available; 1 patient underwent renal transplantation and remains clinically well taking anakinra, and in the remaining 3 patients, anakinra therapy resulted in remission of their nephrotic syndrome.
Conclusions Anakinra therapy was well tolerated and has sustained efficacy on dermatologic and rheumatic manifestations in these patients with CIAS-1/NALP3 mutations. This treatment also resulted in resolution of AA amyloidosis–associated nephrotic syndrome in all affected patients.
Author Affiliations: Department of Dermatology, University of California, San Francisco (Dr Leslie); National Amyloidosis Centre (Drs Lachmann, Bybee, and Hawkins and Ms Gallimore) and Centre for Paediatric and Adolescent Rheumatology, Windeyer Institute (Dr Woo), Royal Free & University College Medical School, and Genetic Skin Disease Group, St John's Institute of Dermatology, Guy’s, King's and St Thomas' School of Medicine (Ms Bruning and Dr McGrath), London, England; and Departments of Pathology (Dr Roberts) and Dermatology (Dr Grattan), Norfolk and Norwich University Hospital, Norwich, England.
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
New CIAS1 mutation and anakinra efficacy in overlapping of Muckle-Wells and familial cold autoinflammatory syndromes
Maksimovic et al.
Rheumatology (Oxford) 2008;47:309-310.
ABSTRACT
| FULL TEXT
Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2007
Furst et al.
Ann Rheum Dis 2007;66:iii2-iii22.
FULL TEXT
|
