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

Tamar Veres,Yoel Levinsky,Gabriel Chodick,Yonatan Butbul Aviel,Nofar Hezkelo,Riva Brik,Sabreen Abu Ahmad,Orly Ohana,Gil Amarilyo,Maryam Abu Rumi

doi:10.3389/fped.2021.800656

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+.

Highlights

PFAPA is an acronym for periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome
We have previously reported that 18.7% of patients diagnosed with PFAPA had a concomitant diagnosis of Familial Mediterranean fever (FMF) (3)
The 216 PFAPA patients were divided into two groups: the FH− group (N = 185), where patients did not have any family members with a known diagnosis of PFAPA, and the FH+ group (N = 31) where each patient had at least one family member with a known diagnosis of PFAPA

Summary

Introduction

PFAPA is an acronym for periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome. PFAPA, the most common periodic fever syndrome in children, typically presents before the age of 5 years with fevers over 38.9◦C (102◦F) that last from a few days to a week and recur every 3 to 8 weeks. These fevers are accompanied by either one or more of the following symptoms: aphthous ulcers— small, relatively painless lesions on the tongue and oral mucosa, pharyngitis with or without white exudates on the tonsils, and swollen cervical lymph nodes (adenitis). Another study demonstrated that in a cohort of 393 children who fulfilled the diagnostic criteria for PFAPA, approximately 20% tested positive for a mutation in either the MVK, TNFRSF1A, or MEFV genes (2)

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