Profile of blood cells and inflammatory mediators in periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome

A cohort of patients with a median age of 4.9 years experiencing 'typical PFAPA' episodes participated in this study. Blood cells and serum cytokines were analyzed by CBC analysis and multiplex ELISA.Oscillations in the concentration of blood cells during the afebrile and febrile phases of typical PFAPA syndrome were observed; novel findings include increased monocytes and decreased eosinophils during a febrile episode and increased thrombocytes in the afebrile interval. Relatively modest levels of pro-inflammatory cytokines were present in sera. IFNγ-induced cytokine IP10/CXCL10 was increased after the onset of fever while T cell-associated cytokines IL7 and IL17 were suppressed during afebrile and febrile periods.Identification of dysregulated blood cells and serum cytokines is an initial step towards the identification of biomarkers of PFAPA disease and/or players in disease pathogenesis. Future investigations are required to conclusively discern which mediators are associated specifically with PFAPA syndrome.The periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome was originally described by Marshall et al in 1987 and the acronym, PFAPA, was coined two years later together with the diagnostic criteria [1,2]. PFAPA syndrome is regarded as a non-hereditary disease of unknown etiology although the clinical observation is that, in a small proportion of cases, one of the parents or a more distant relative had similar symptoms in childhood [3]. The actual incidence of PFAPA syndrome in the pediatric population is not known but it is more common than the hereditary periodic fevers, except in populations with an ethnic origin in the Eastern Mediterranean basin where FMF is more common. Every pediatrician is likely to encounter at least one case of PFAPA during his or her career [4]. Autoinflammatory attacks in PFAPA syndrome occur within a 2-8 week interval with remarkable clockwork periodicity in approximately 50% of patients [3,5,6].