P02-023 - NLRP3 mosaicism as a cause of late-onset CAPS

The dominantly inherited cryopyrin-associated periodic syndromes (CAPS) are caused by heterozygous missense gain-of-function mutations in the NLRP3 (CIAS1) gene encoding NLRP3 (also known as cryopyrin). Most patients present at a young age with a variety of clinical symptoms including fevers, urticaria-like skin rash, arthropathy, and CNS inflammation. A subset of patients followed at the National Institute of Health’s autoinflammatory disease clinic has adult-onset fevers and urticarial rash but conventional genetic testing has been unremarkable for any mutations in NLRP3. We analyzed one such "mutation-negative" patient. She is a 63y/o female of Irish ancestry who developed a gradually worsening stress-induced urticarial rash in her 40s. Additional clinical history is remarkable for severe arthralgia, myalgia, chills, and occasional conjunctivitis. Initially started on anakinra 100mg/day in 2003, she had dramatic improvement in symptoms; however, her anakinra dose has required periodic adjustments since that time to control her symptoms.