Familial Periodic Fever, Aphthous Stomatitis, Pharyngitis and Adenitis (PFAPA) Syndrome; is it a Separate Disease?

Abstract

Introduction: PFAPA is the most common periodic fever syndrome in the pediatric population yet pathogenesis is unknown. PFAPA was believed to be sporadic but family clustering has been widely observed.Objective: To identify demographic and clinical differences between patients with PFAPA and a positive family history (FH+) compared to those with PFAPA with no family history (FH-).Methods: In a database comprising demographic and clinical data of 273 pediatric PFAPA patients treated at two tertiary centers in Israel, 31 (14.3%) of patients were PFAPA FH+. Data from patients with FH+ for PFAPA was compared to data from those with FH- of the disorder. Furthermore, family members (FMs) of those with FH+ were contacted via telephone for more demography and clinical details. Results: FH+ group had more headaches (32% vs.2%; p= 0.016), myalgia (56% vs. 19%; p= 0.001), higher carrier frequency of M694V mutation (54% vs. 25%; p=0.053), greater family history of FMF (30% vs. 15%; p=0.096) and better outcomes with colchicine (82% vs. 52%; p=0.096) compared to those with FH-. FMs displayed almost identical characteristics to the FH+ group except for greater arthralgia during flares (64% vs. 23%; p=0.008) and compared to the FH- group, more oral aphthae (68% vs. 43%; p=0.002), myalgia/arthralgia (64% vs. 19%/16%; p<0.0001), and higher rates of FH of FMF (45% vs.15%; p=0.003). Conclusions: Our findings suggest that FH+ likely experience a different subset of disease with higher frequency of family history of FMF, arthralgia, myalgia and better response to colchicine compared to FH-. Colchicine prophylaxis for PFAPA should be considered in FH+.