Efficacy of anti-IL-1 treatment in Majeed syndrome.
Ann Rheum Dis
; 72(3): 410-3, 2013 Mar.
Article
em En
| MEDLINE
| ID: mdl-23087183
ABSTRACT
BACKGROUND AND OBJECTIVE:
Majeed syndrome is an autosomal recessive disorder characterised by the triad of chronic recurrent multifocal osteomyelitis, congenital dyserythropoietic anaemia and a neutrophilic dermatosis that is caused by mutations in LPIN2. Long-term outcome is poor. This is the first report detailing the treatment of Majeed syndrome with biological agents and demonstrates clinical improvement with IL-1blockade.METHODS:
We describe the clinical presentation, genetic analysis, cytokine profiles and response to biological therapy in two brothers with Majeed syndrome.RESULTS:
Both boys were homozygous for a novel 2-base pair deletion in LPIN2 (c.1312_1313delCT; p.Leu438fs+16X), confirming the diagnosis. Their bone disease and anaemia were refractory to treatment with corticosteroids. Both siblings had elevated proinflammatory cytokines in their serum, including tumour necrosis factor α (TNF-α), however a trial of the TNF inhibitor etanercept resulted in no improvement. IL-1 inhibition with either a recombinant IL-1 receptor antagonist (anakinra) or an anti-IL-1ß antibody (canakinumab) resulted in dramatic clinical and laboratory improvement.CONCLUSIONS:
The differential response to treatment with TNF-α or IL-1 blocking agents sheds light into disease pathogenesis; it supports the hypothesis that Majeed syndrome is an IL-1ß dependent autoinflammatory disorder, and further underscores the importance of IL-1 in sterile bone inflammation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteomielite
/
Proteínas Nucleares
/
Interleucina-1
/
Antirreumáticos
/
Anemia Diseritropoética Congênita
Limite:
Child, preschool
/
Humans
/
Infant
/
Male
Idioma:
En
Revista:
Ann Rheum Dis
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Dinamarca