Familial Periodic Fever, Aphthous Stomatitis, Pharyngitis and Adenitis Syndrome; Is It a Separate Disease?

Abstract

IntroductionPeriodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA) is the most common periodic fever syndrome in the pediatric population, yet its pathogenesis is unknown. PFAPA was believed to be sporadic but family clustering has been widely observed.ObjectiveTo identify demographic and clinical differences between patients with PFAPA and a positive family history (FH+) as compared to those with no family history (FH−).MethodsIn a database comprising demographic and clinical data of 273 pediatric PFAPA patients treated at two tertiary centers in Israel, 31 (14.3%) had FH+. Data from patients with FH+ were compared to data from those with FH−. Furthermore, family members (FMs) of those with FH+ were contacted via telephone for more demographic and clinical details.ResultsThe FH+ group as compared to the FH− group had more myalgia (56 vs. 19%, respectively, p = 0.001), headaches (32 vs. 2%, respectively, p = 0.016), and a higher carrier frequency of M694V mutation (54% vs. 25%, respectively, p = 0.05). Colchicine was seen to be a more beneficial treatment for the FH+ group as compared to the FH− group; however, with no statistical significance (p = 0.096). FMs displayed almost identical characteristics to patients in the FH+ group except for greater arthralgia during flares (64 vs. 23%, respectively, p = 0.008), and compared to the FH− group they had more oral aphthae (68 vs. 43%, respectively, p = 0.002), myalgia/arthralgia (64 vs. 19%/16%, respectively, p < 0.0001), and higher rates of FH of Familial Mediterranean fever (FMF) (45 vs.15%, respectively, p = 0.003).ConclusionsOur findings suggest that patients with a FH+ likely experience a different subset of disease with higher frequency of family history of FMF, arthralgia, myalgia, and might have a better response to colchicine compared to FH−. Colchicine prophylaxis for PFAPA should be considered in FH+.

Health conditions of first-degree relatives of children with familial Mediterranean fever

“…PFAPA was previously shown to be highly related with FMF genetically and shares many common features with FMF which may cause a diagnostic challenge. [29][30][31] Tonsillectomy and adenoidectomy seem to be curative treatment options in most patients with PFAPA. 32 Although there were only 2 FDRs with PFAPA in the FMF group, we hypothesize that a significant amount of them were undiagnosed in the past, due to the newly growing and currently insufficient awareness of PFAPA among clinicians in our country.…”

Recurrent Fever with Oral Lesions in Egyptian Children: A Familial Mediterranean Fever Diagnosis Not to Be Missed

“…Current data from the literature reported a significant overlap between FMF and PFAPA which have characteristic oral lesions [ 13 , 14 , 15 , 16 , 17 ]. Moreover, Butbul Aviel and colleagues [ 18 ] demonstrated that PFAPA and FMF, two frequent autoinflammatory disorders, are closely correlated in individuals of Mediterranean descent [ 18 ].…”