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Purpose PFAPA syndrome is a benign, recurrent inflammatory disease of childhood. Tonsillectomy is one of the therapeutic options with a yet unexplained biological mechanism. We tested whether specific lymphocyte subsets recruited from blood to human tonsils participate in PFAPA pathogenesis. Methods Paired tonsils/peripheral blood (PB) samples were investigated (a) from children with PFAPA that successfully resolved after tonsillectomy ( n = 10) (b) from children with obstructive sleep apnoea syndrome as controls ( n = 10). The lymphocyte profiles were analysed using 8-colour flow cytometry, immunoglobulin (IGH) and T-cell receptor (TCR) gene rearrangements via PCR and next generation sequencing; a TREC/KREC analysis was performed using qPCR. Results The PFAPA tonsils in the asymptomatic phase had a lower percentage of B-lymphocytes than controls; T-lymphocyte counts were significantly higher in PB. The percentages of cytotoxic CD8pos T-lymphocytes were approximately 2-fold higher in PFAPA tonsils; the transitional B cells and naive stages of both the CD4pos and CD8pos T-lymphocytes with a low expression of PD-1 molecule and high numbers of TREC were also increased. With the exception of elevated plasmablasts, no other differences were significant in PB. The expression levels of CXCL10, CXCL9 and CCL19 genes were significantly higher in PFAPA tonsils. The IGH/TCR pattern showed no clonal/oligoclonal expansion. DNA from the Epstein-Barr virus, Human Herpervirus-6 or adenovirus was detected in 7 of 10 PFAPA tonsils but also in 7 of 9 controls. Conclusions Our findings suggest that the uninhibited, polyclonal response of newly derived lymphocytes participate in the pathogenesis of PFAPA. Because most of the observed changes were restricted to tonsils and were not present in PB, they partly explain the therapeutic success of tonsillectomy in PFAPA syndrome.

BackgroundPertussis infection has been recognized as a global cause of morbidity and mortality, especially amongst infants in the first months of life. The most severe course of infection is seen in unvaccinated infants, who can develop life-threatening complications.Case Presentation SummaryA 6 week-old boy was admitted to PICU from a local hospital due to respiratory collapse. The diagnosis of pertussis was made 1 week after initial symptoms including coughing, and he started a 10-day course of erythromycin, 4 days after which he was admitted to our PICU. Despite treatment with azithromycin and cefotaxime, he deteriorated clinically, developing pronounced leukocytosis. While in extremis he obtained two blood exchange transfusions and intravenous immunoglobulin with good clinical effect. The pertussis strain identified showed resistance to erythromycin, clarithromycin and azithromycin. The bacteria had good sensitivity to trimethoprim-sulfamethoxazole and he was therefore given this treatment for 19 days. The total length of antibiotic treatment was 23 days. The patient required invasive mechanical ventilation and high-flow nasal therapy (Optiflowu00ae) for 16 days and 11 days respectively. On day 25 he could be transferred to the standard paediatric department.His mother had not been vaccinated in childhood, and developed similar symptoms few weeks before him.Learning Points/DiscussionThe vaccination of pregnant women, which is well described, can significantly decrease the severe courses of pertussis infection in neonates and infants. Usual treatment of pertussis with antibiotics can fail due to bacterial resistance. Blood exchange transfusion is an important therapy to consider in severe cases of pertussis infection with significant leukocytosis.