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

Abstract

BackgroundThis study aimed to profile levels of blood cells and serum cytokines during afebrile and febrile phases of periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome to advance pathophysiological understanding of this pediatric disease.MethodsA 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.ResultsOscillations 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.ConclusionsIdentification 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.

Marshall syndrome – a challenge in medical practice

“…This indicates that an association of high serum CRP with elevated leukocyte count and undetectable levels of procalcitonin could be used to distinguish PFAPA attack from bacterial infection (10). The levels of the proinfl ammatory cytokine TNF-α were elevated during and between PFAPA episodes, an observation that suggests dysregulation of the immune response in PFAPA syndrome, with continuous proinfl ammatory cytokine activation (7,17).…”

PFAPA syndrome in siblings. Is there a genetic background?

“…These tests include throat culture, chest radiography, complete blood counts, erythrocyte sedimentation rate (ESR), CRP, immunoglobulin (IgA, IgM, IgG, and IgD) quantification, C3, C4, CH50, Epstein-Barr virus, CMV, Toxoplasma, and adenovirus serology. These analyses are usually negative except for mild leukocytosis and an elevated CRP or ESR during febrile attacks [3,8]. Procalcitonin concentrations are usually within normal limits [22].…”

Syndrome PFAPA : ce que nous a appris la cohorte Européenne

“…Quelques travaux récents ont étudié la physiopathogénie du syndrome PFAPA, en particulier la sécrétion de cytokines. Pendant les poussées, une neutrophilie, une monocytose et une lymphopénie relative sont observées, ainsi qu'une augmentation du taux de CRP et de sérum amyloïde A [16]. On retrouve également une surexpression des gènes en lien avec l'IL-1 et activés par l'interféron-gamma, ainsi qu'une augmentation de l'IL-6, de l'IL-8 et des chémokines pour les lymphocytes T activés.…”