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

PFAPA is the most common periodic fever syndrome in the pediatric population yet pathogenesis and genetics is unknown. PFAPA was believed to be sporadic but current research indicates heredity. This study attempts to identify differences between PFAPA patients with (FH+) and without family history (FH-) in order to determine the existence of heritable and sporadic subtypes. 31/273 (14.3%) of PFAPA patients from a large Israeli database were found to have FH+, and their data was compared to those with FH-. Data was also collected from family members (FMs) of FH+ and compared to FH- and FH+. Those with FH+ had more headaches (32% vs. 12%; 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 experienced 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). Not enough evidence exists to state that those with FH+ and FH- have different subsets of PFAPA. Further exploration of increased rates of M694V mutations in FH+ is warranted and genetic testing for FMs can help clarify this association. Colchicine prophylaxis for PFAPA attacks should be considered in FH+ especially for carriers of MEFV mutation(s).