Deficiency of the Interleukin-1 Receptor Antagonist (DIRA)

Abstract

Deficiency of the interleukin-1 receptor antagonist IL-1Ra (DIRA) is a very rare and severe autoinflammatory disease associated with loss of function mutations in the IL1RN gene. Inflammation results from unopposed signaling by IL-1α and IL-1β. DIRA presents mostly in the neonatal period with systemic inflammation and characteristic skin pustulosis and multifocal osteomyelitis. Other features include premature birth, fever, arthritis, ballooning of epiphysis, periostitis, widening of ribs, osteopenia, and less frequent internal organ involvement with CNS vasculitis, interstitial lung disease, large vein thrombosis, and hepatosplenomegaly. The severe inflammation can lead to respiratory distress and systemic inflammatory response syndrome with a 25% mortality. Long-term sequelae include joint contractures and deformities, muscle atrophy, growth retardation, and developmental delay. The disease is highly and rapidly responsive to IL-1 blockade.