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Efficacy of anti-IL-1 treatment in Majeed syndrome
  1. Troels Herlin1,
  2. Bente Fiirgaard2,
  3. Mette Bjerre3,
  4. Gitte Kerndrup4,
  5. Henrik Hasle1,
  6. Xinyu Bing5,
  7. Polly J Ferguson5
  1. 1Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark
  2. 2Department of Radiology, MR Research Centre, Aarhus University Hospital, Aarhus, Denmark
  3. 3Medical Research Lab, Aarhus University Hospital, Aarhus, Denmark
  4. 4Clinical Genetics Department, Vejle Hospital, Vejle, Denmark
  5. 5Department of Pediatrics, University of Iowa, Carver College of Medicine, Iowa City, Iowa, USA
  1. Correspondence to Dr Polly J Ferguson, Department of Pediatrics, University of Iowa, 200 Hawkins Drive, 4038 Boyd Tower, Iowa City, IA 52242, USA; polly-ferguson{at}


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-1β 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-1β dependent autoinflammatory disorder, and further underscores the importance of IL-1 in sterile bone inflammation.

  • Fever Syndromes
  • DMARDs (biologic)
  • Gene Polymorphism
  • Inflammation
  • Cytokines

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