[Clinical and genetic analysis of 11 cases with periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome].

Objective: To investigate the clinical, inflammatory and genetic characteristics of cases with periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome. Methods: Clinical and inflammatory manifestations and gene sequencing of 11 cases with PFAPA were retrospectively analyzed. Inflammatory markers including white blood cell (WBC) , C reactive protein (CRP) , and serum amyloid A (SAA) were compared between febrile period and intermittent period. Fifteen normal children were taken as healthy controls. The levels of plasma inflammatory cytokines including interleukin(IL)1beta, IL-6, IL-17, tumor necrosis factor(TNF)-alpha, interferon (IFN)-gamma, and granulocyte-colony stimulating factor(G-CSF) were compared between febrile period and intermittent period with paired-sample t test, and compared between febrile cases and healthy controls with independent t test. Results: A total of 11 cases (7 females and 4 males) were included. The median onset age was 24 (3-60) months, and the median age of diagnosis was 69 (11-151) months. The median febrile duration was 4 (1-8) days, and the intermittent period lasted 1 to 8 weeks. All the cases had periodic fever and pharyngitis/tonsillitis, 7 of whom had combined lymphadenitis, and 5 of whom suffered from oral ulcers. Compared to intermittent-period-status,WBC ((14.7+/-4.1) x10(9)/L vs. (8.4+/-1.9) x10(9)/L, P<0.05), CRP((24.2+/-21.1) vs. (3.3+/-2.1)mg/L, P<0.05), SAA ((136.4+/-47.7) vs. (7.1+/-1.1)mg/L, P<0.05) were significantly elevated in febrile period. Compared to intermittent-period-status and healthy controls, plasma levels of IL-6 ((38+/-10) vs. (8+/-4) and (8+/-5)ng/L, t=6.514 and 6.830 respectively, P<0.05), IFN-gamma ((132+/-43) vs.(49+/-21) and (53+/-21)ng/L, t=4.069 and 4.276 respectively, P<0.05), G-CSF ((403+/-12) vs. (175+/-90) and (121+/-49)ng/L, t=4.219 and 9.047 respectively, P<0.05) were significantly higher in febrile period, while no differences were found in levels of IL-1beta, IL-17 and TNF-alpha. Gene sequencing found MEFV gene heterozygous variation in 8 cases. Conclusions: PFAPA often manifests as periodic fever, pharyngitis, tonsillitis, aphthous stomatitis and adenitis. Gene sequencing analysis, detection of inflammation markers and cytokines could help with the diagnose of this disease.