Background/Purpose: The Periodic Fever Syndromes (PFS) are a rapidly expanding group of disorders primarily of the innate immune system that often affect the inflammasome. In our previous report (ACR 2014 Annual Meeting), we detailed 30 patients with about 1/3 with Periodic Fever, Aphthous Stomatitis, Pharyngitis and Adenopathy (PFAPA), 1/3 with a genetically defined PFS, and 1/3 unclassifiable. We now report with improved genetic testing (Medical Neurogenetics NextGen PFS Panel – 37 genes) novel phenotypic expressions of genetically determined PFS in 15 patients.

Methods: Case acquisition was performed by three methods: 1) review of ICD 9/10 coded records for Familial Mediterranean Fever (ICD 9 277.31); 2) laboratory test records for PFS genetic screening; and 3) clinic records between 1/1/2011 and 12/31/2017 after receiving approval from the Institutional Review Board for a de-identified retrospective case analysis.

Results: Twenty seven cases (12 female and 15 male) were obtained that underwent extensive clinical evaluation including PFS genetic screening. Clinical diagnoses included FMF (10), Muckle Wells (2), TRAPS (4), and HIDS (1). Other diagnoses included Crohn’s (1), SoJIA (1), FUO (1), PFAPA (6), and cold induced urticaria (1). Of these 27 cases, 15 were subsequently associated with a genetic cause. Seven of the 10 FMF cases were confirmed genetically, all of whom were either heterozygous or compound heterozygotes. Both cases of Muckle Wells had non classical genetics – one was a compound heterozygote for CIAS 1, and the other had a mutation in the NOD gene. Both TRAPS cases were atypical – one was asymptomatic, and the other developed SLE. Two patients had novel syndromes. One TRAPS patient had a mutation in the TNFRSF-1A gene who eventually remitted with IVIG after failing multiple drugs. The other had SoJIA with a mutation in the LPIN 2 gene but responded to colchicine. Only 1 of the 15 genetically proven cases had a classical presentation and classical genetics (HIDS secondary to a mutation in the MVK gene).

Conclusion:  Most patients presented atypically both from a clinical and genetic standpoint, making treatment challenging and difficult. Genetic testing with PFS screen was helpful in over ½ of the cases to develop therapeutic treatment plans. Given the atypical clinical presentations seen with genetically determined PFS, extensive genetic testing is indicated for all patients presenting with a PFS except those with a classical PFAPA syndrome.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/novel-insights-into-periodic-fever-syndromes/