LB1040 Treatment of sweet syndrome by molecular identification of PIK3R1 mutation

Acute febrile neutrophilic dermatosis (Sweet syndrome) is a potentially fatal multiorgan inflammatory disease characterized by fever, leukocytosis, and rash with infiltrate. Disease pathophysiology remains elusive. Corticosteroids steroid sparing agents remain mainstays of treatment, but refractory cases pose clinical challenge. Whole genome sequencing transcriptomic profiling Sweet syndrome patient identified elevated IL-1 signaling in lesional skin caused PIK3R1 gain-of-function mutation neutrophils. Targeted treatment an IL-1R1 antagonist resulted dramatic therapeutic response enabled tapering corticosteroids. Molecular study this improved our understanding guided therapy.