Ear Surgery and Otitis Media (38)
Pediatric Urology and Nephrology Studies (32)
Respiratory viral infections research (31)
Pediatric health and respiratory diseases (29)
Pneumonia and Respiratory Infections (23)
Lantto U, Tapiainen T, Pokka T, Koivunen P, Helminen M , et al.
The Laryngoscope •
Tonsillectomy is an effective treatment for periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome. Tonsillotomy has a milder operative risk profile and postoperative morbidity in children than tonsillectomy. We aimed to compare the efficacy of tonsillotomy to observation-only in children with PFAPA syndrome at a 3-month follow-up. This was a randomized multicenter trial with sequential design. Participants were randomized into a tonsillotomy group and a control group that was only observed. The trial started in 1/2017 and was accomplished in 12/2021 with 16 patients (10 boys, six girls, the mean age 4.2 years). The symptoms were monitored with daily symptom diaries. After the 3-month follow-up, 7/8 patients (87.5%) in the tonsillotomy group and 2/8 (25%) patients in the control group were free from PFAPA symptoms (95% CI 13% to 87%; p = 0.0021). The mean number of days with fever was 2.6 (SD 3.7) in the tonsillotomy group and 8.0 (SD 6.5) days in the control group (n = 8) (p = 0.06). Mean number of fever days compatible with PFAPA syndrome was 0.8 (SD 1.4) in the tonsillotomy group and 6.5 (SD 6.0) in the control group (95%CI -10% to -1%; p = 0.007). Rescue tonsillectomy was needed for all patients in the control group and none of the patients in the tonsillotomy group. Tonsillotomy might be an effective treatment option for children with PFAPA syndrome. Further studies are needed to clarify the long-term efficacy of tonsillotomy for treating PFAPA. 2 Laryngoscope, 134:968-972, 2024.
Tejesvi MV, Tapiainen T, Vänni P, Uhari M, Suokas M , et al.
Frontiers in cellular and infection microbiology •
Periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome (PFAPA) is the most common periodic fever syndrome in children with unknown etiology, effectively treated with tonsillectomy. Earlier we have shown that tonsil microbiome is different in patients with PFAPA as compared to that in controls. Recently, fungal microbiome, mycobiome, has been linked to the pathogenesis of inflammatory diseases. We now investigated the role of mycobiome of tonsils in PFAPA. Random forest classification, a machine learning approach, was used for the analysis of mycobiome data. We examined tonsils from 30 children with PFAPA and 22 control children undergoing tonsillectomy for non-infectious reasons. We identified 103 amplicon sequence variants, mainly from two fungal phyla, Ascomycota and Basidiomycota. The mean relative abundance of in the tonsil mycobiome was 11% (95% CI: 19 to 27%) in cases and 3.4 % (95% CI: -0.8% to 8%) in controls, p =0.104. Mycobiome data showed no statistical difference in differentiating between PFAPA cases and controls compared to a random chance classifier (area under the curve (AUC) = 0.47, SD = 0.05, p = 0.809). In conclusion, in this controlled study, tonsillar mycobiome in children with PFAPA syndrome did not differ from that of the controls.
Kettunen S, Lantto U, Koivunen P, Tapiainen T, Uhari M , et al.
European journal of pediatrics •
The etiology and pathogenesis of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome are unclear. We performed a case-control study to evaluate potential environmental or lifestyle factors associated with PFAPA morbidity. We enrolled 119 patients with PFAPA syndrome who had undergone tonsillectomy in Oulu University Hospital between 1987 and 2007. We recruited 230 controls, matched for sex, birth date, and place from the database of the Population Register Center of Finland. All the patients and controls completed a questionnaire regarding exposure to environmental triggers during early childhood. Maternal smoking was more common among PFAPA syndrome patients than controls (23 vs. 14%; P = 0.005). PFAPA patients had lower breastfeeding rates than controls (94 vs. 99%; P = 0.006). No other environmental factors were associated with PFAPA syndrome, except having an aquarium at home (P = 0.007). The patient group also used natural or herbal medicines more often than the controls (P = 0.01). Maternal smoking and lack of breastfeeding, known risk factors for common childhood infections, were more common in patients with PFAPA syndrome than in matched controls. Environmental factors may be important in the pathogenesis of PFAPA syndrome and should be evaluated in future studies. What is Known: • The pathogenesis and genetics of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome remain unsolved. • PFAPA syndrome has been shown to cluster in families. What is New: • Maternal smoking and lack of breastfeeding are more common in patients with PFAPA syndrome than in the controls. • Environmental risk factors may be important in the pathogenesis of the syndrome.
Lantto U, Kettunen S, Tapiainen T, Koivunen P, Uhari M , et al.
Clinical and experimental rheumatology •
To compare the long-term morbidity of patients with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome treated by tonsillectomy (TE) in childhood to that of matched controls. We identified 132 PFAPA patients from the medical records treated by TE in 1987-2007 in Oulu University Hospital, Finland. Altogether 119 patients participated the follow-up study and 94 were clinically examined on average 9.0 years after TE. The controls consisted of 230 randomly selected age-, sex-, and birth place-matched individuals from the Population Register Center of Finland. The patients and controls completed a detailed questionnaire about their current health and the data were compared. Self-estimated general health was good and growth was normal among PFAPA patients and controls at long-term follow-up. There were no between-group differences in the occurrence of autoimmune or other chronic diseases. Thirty percent of the PFAPA patients and 13% of the controls reported infections as causes of hospital visits during their lifetime (p<0.001). Usage of antibiotics during lifetime was reported by 99% of the PFAPA patients and by 88% of the controls (p= 0.009). Twelve percent of PFAPA patients and 0.4% of the controls reported oral thrush in their history (p=0.003). The health of the PFAPA patients was as good as that of healthy matched controls. Autoimmune or other chronic diseases were not more prevalent among PFAPA patients treated with TE in childhood than among controls. Respiratory infections and oral thrush were more common among the PFAPA patients than controls.
Tejesvi MV, Uhari M, Tapiainen T, Pirttilä AM, Suokas M , et al.
European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology •
Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) is a childhood febrile syndrome of unknown origin that is often cured with tonsillectomy. We aimed to compare the bacterial microbiota of the tonsils removed from PFAPA patients with those of controls. We used next-generation sequencing technology to investigate the bacterial microbiota of the tonsils of 30 PFAPA patients and 24 controls. We found significant differences in the presence and relative abundance of many bacteria between PFAPA cases and controls. For example, cyanobacteria, potential producers of microcystins and other toxins, were more common in the case samples (14/30, 47 %) than in the controls (4/24, 17 %, p = 0.02), and the mean relative abundance of cyanobacteria was higher in the case samples (0.2 %) than in the controls (0.01 %, p = 0.01). Streptococci were present in all samples in both groups, but their mean relative abundance was lower in the case samples (3.7 %) than in the controls (9.6 %, p = 0.01). Typical nasopharyngeal microbes such as fusobacteria, Prevotella, Tannerella, Porphyromonas, and Parvimonas dominated the microbiota of the tonsils in both groups. The microbiota of the tonsils removed from PFAPA patients differed significantly from those of the controls. Tonsillar microbiota may play a role in triggering the inflammatory processes that lead to symptoms of PFAPA.
Lantto U, Koivunen P, Tapiainen T, Glumoff V, Hirvikoski P , et al.
APMIS : acta pathologica, microbiologica, et immunologica Scandinavica •
Periodic Fever, Aphtous stomatitis, Pharyngitis, and Adenitis (PFAPA) is a childhood febrile syndrome that is often cured by tonsillectomy (TE). We hypothesized that microbes present in the tonsils may act as a trigger for the activation of inflammasomes and investigated the microbiology of the tonsils in PFAPA patients and controls. We recruited 31 consecutive children who underwent TE due to PFAPA; 24 children who underwent TE due to other reasons served as controls. We cultured all the samples for bacteria, mycobacteria, yeasts, and viruses and used PCR for 15 viruses. Also biofilm formation and histologic findings were identified. The samples of the patients yielded Candida albicans more often than did the controls (16 vs 0%, p = 0.003). Staphylococcus aureus occurred in only 10% of the patients, but in 38% of the controls (p = 0.01). Varicella zoster and Herpes simplex viruses occurred less often in patients than in controls. Biofilm was present in 55% of PFAPA tonsils, but in only 24% of the controls (p = 0.03). The microbes found in the tonsils of PFAPA patients showed significant differences from those of controls. This may in part explain the efficacy of TE in PFAPA.
Renko M, Salo E, Putto-Laurila A, Saxen H, Mattila PS , et al.
The Journal of pediatrics •
We carried out a prospective, randomized, controlled trial to clarify the effect of tonsillectomy on the clinical course of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome. Twenty-six consecutive children (mean age 4.1 years) with at least 5 PFAPA attacks were recruited from 3 tertiary care pediatric hospitals during 1999-2003 and randomly allocated to tonsillectomy or follow-up alone. They were all followed up with symptom diaries for 12 months. Tonsillectomy was allowed after 6 months in the control group if the attacks recurred. Six months after randomization all 14 children in the tonsillectomy group and 6/12 children in the control group (50%) were free of symptoms (difference 50%, 95% confidence interval 23% to 75%, P < .001). Tonsillectomy was performed on 5/6 of the patients in the control group who still had symptoms after 6 months. The remaining unoperated child in the control group had recurrences of the fever episodes throughout the follow-up, but the symptoms became less severe, and the parents did not choose tonsillectomy. Tonsillectomy appeared to be effective for treating PFAPA syndrome. The fever episodes ceased without any intervention in half of the control subjects. We conclude that although the mechanisms behind this syndrome are unknown, tonsillectomy can be offered as an effective intervention for children with PFAPA.