The first reported case of compound heterozygous IL1RN mutations causing deficiency of the interleukin‐1 receptor antagonist

Interleukin‐1 receptor antagonist (IL‐1Ra) deficiency is a rare autoinflammatory disease involving neonatal onset of pustulosis, periostitis, and sterile osteomyelitis. We report the case of a 2‐week‐old male who presented with a swollen, erythematous left index finger and elevated serum markers of inflammation. He later developed cyclical fevers, diffuse pustular skin lesions, and thrombus formation. After not responding to broad‐spectrum antimicrobial therapy and achieving only moderate success with systemic steroid therapy, he was ultimately treated with recombinant IL‐1Ra, anakinra, and experienced significant clinical improvement. Sequencing of his IL1RN gene revealed that the patient was compound heterozygous for a known mutation (E77X) associated with IL‐1Ra deficiency and a novel mutation in exon 2 of the gene (c.140delC; p.T47TfsX4). His case highlights IL‐1Ra deficiency as an autoinflammatory disease that is distinct from neonatal‐onset multisystem inflammatory disease but that also responds well to anakinra. Our patient is the first reported compound heterozygote for E77X and the novel mutation in exon 2 of the gene, the latter of which adds to what will surely be a growing database of pathologic mutations in IL1RN.