Interleukin-36 receptor antagonist deficiency patient with a novel mutation

The deficiency of interleukin-36 receptor antagonist (DITRA) is a monogenic autoinflammatory condition associated with generalized pustular psoriasis (GPP). Diagnostic criteria and treatment recommendations for DITRA are inadequate. The diagnosis is established by detecting a biallelic loss-of-function mutation in IL36RN, which leads to activation of the IL36 pathway.

We present a pediatric case of GPP with a novel IL36RN mutation that supports the diagnosis of DITRA. In patients with DITRA unresponsive to IL-1 targeted therapies, favorable results may be achieved with the administration of TNF-α inhibitors, particularly IL-36 pathway inhibitors. Twenty-nine papers, encompassing 55 pediatric cases, were synthesized to contextualize treatment responses.

Novel DITRA-associated mutations continue to be discovered. Given the rarity of the disease, it will be possible to reveal the genotype-phenotype relationship in the future with the publication of larger DITRA case series.