Microbes of the tonsils in PFAPA (Periodic Fever, Aphtous stomatitis, Pharyngitis and Adenitis) syndrome - a possible trigger of febrile episodes

Abstract

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.

Towards better diagnostic criteria for periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome

“…Since the signs of inflammation in PFAPA often localise in the pharyngotonsillar region, and tonsillectomy has been shown to be an effective treatment for the syndrome , the palatine tonsils have been a logical focus of research. The histology of palatine tonsils in PFAPA has not shown significant differences when compared to tonsil tissues removed for other reasons , but the distribution of both B‐ and T‐lymphocytes and the production of pro‐ and anti‐inflammatory cytokines seem to be different . Tonsils removed from PFAPA patients have revealed smaller amounts of B‐lymphocytes and more naive polyclonal T‐lymphocytes when compared to tonsils removed for other reasons .…”

“…With routine clinical microbiology, the throat or tonsillar samples of PFAPA patients have revealed no evident viruses or bacteria responsible for the symptoms . However, unspecific biofilms and Candida albicans were found more often and Staphylococcus aureus less often in tonsil samples removed from PFAPA patients compared to controls .…”

“…The trigger of the febrile response and cytokine production in PFAPA is not known, but host–microbe interaction has been considered to be the most likely possibility . With routine clinical microbiology, the throat or tonsillar samples of PFAPA patients have revealed no evident viruses or bacteria responsible for the symptoms . However, unspecific biofilms and Candida albicans were found more often and Staphylococcus aureus less often in tonsil samples removed from PFAPA patients compared to controls .…”

Risk factors for periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome: a case-control study

“…Cloacibacterium was isolated only from PFAPA patients' tonsils (6,7). The results suggest that microbial activity, together with exposure to various triggers, such as maternal smoking, with known immunomodulatory effects may lead to the development of PFAPA syndrome.…”

“…Recent studies support the hypothesis that PFAPA syndrome involves inflammasome-driven proinflammatory interleukin (IL)-1β production during febrile episodes (4,5). Inflammasomes may be activated by microbes or other environmental stimuli (6,7). Recent studies showed clear family clustering of PFAPA syndrome (8)(9)(10)(11).…”