Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome.

Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome, the most common periodic disorder of childhood, presents with the cardinal symptoms of periodic fever, aphthous stomatitis, pharyngitis, and adenitis typically before age 5. This review presents the recent literature on PFAPA and summarizes key findings in the pathogenesis, evaluation, and treatment of the disease. Theories surrounding the pathogenesis of PFAPA include a faulty innate immunologic response in conjunction with dysregulated T-cell activation. A potential genetic link is also under consideration. Mediterranean fever (MEFV) gene variants have been implicated and appear to modify disease severity. In individuals with the heterozygous variant, PFAPA episodes are milder and shorter in duration. Diagnostic criteria include the traditional clinical signs, in addition to the following biomarkers: elevated C-reactive protein in the absence of elevated procalcitonin, vitamin D, CD64, mean corpuscular volume, and other nonspecific inflammatory mediators in the absence of an infectious explanation for fever. Treatment of PFAPA includes tonsillectomy, a single dose of corticosteroids, and, most recently, interleukin 1 blockers such as anakinra, rilonacept, and canakinumab. Tonsillectomy remains the only permanent treatment modality.

Ali NS ，Sartori-Valinotti JC ，Bruce AJ 《-》

[Periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome].

Kusuhara K 《-》

Clinical features and new diagnostic criteria for the syndrome of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis.

The syndrome of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) is a common inflammatory disease that presents with periodic fever. We aimed to establish more specific diagnostic criteria for PFAPA based on the clinical characteristics of PFAPA patients in our directory. The clinical, laboratory, genetic, and family history details of 257 Japanese PFAPA patients treated at our and other affiliated hospitals between April 2000 and April 2018 were analyzed along with quantitative measurements of the number of CD64 molecules on neutrophils, and the levels of serum inflammatory cytokines. The sensitivity and specificity of the criteria were calculated for several diseases. Because recurrent fevers were crucial findings, they were defined as the required criterion. Tonsillitis/pharyngitis with white moss were important accompanying signs. Other symptoms associated with febrile episodes were cervical lymphadenitis with tenderness, aphthous stomatitis, sore throat, vomiting, and headache but not cough. A total of 159 (62%) patients had a family history of recurrent fevers, indicating autosomal dominant inheritance. C-reactive protein levels were extremely elevated during febrile attacks but normal in attack-free periods. Serum immunoglobulin D levels were high in 72 of the 199 tested patients. Oral glucocorticoid and cimetidine were extremely effective in all and 51.6% of the patients, respectively. We defined the above as supportive criteria. These criteria were sensitive and specific enough to distinguish PFAPA from other recurrent fever diseases. Raised serum interferon-γ levels and remarkable CD64 expression on neutrophils during flare-ups were recognized, indicating they contributed to diagnosis. Our new criteria are useful for diagnosing PFAPA.

Takeuchi Y ，Shigemura T ，Kobayashi N ，Nagumo H ，Furumoto M ，Ogasawara K ，Fujii H ，Takizawa M ，Soga T ，Matoba H ，Masumoto J ，Fukushima K ，Migita K ，Ojima T ，Umeda Y ，Agematsu K ... -  《-》

Gray zone in the spectrum of autoinflammatory diseases: familial Mediterranean fever accompanying periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome: single-center experience.

Konte EK ，Haslak F ，Yildiz M ，Gucuyener N ，Ulkersoy I ，Gunalp A ，Aslan E ，Adrovic A ，Sahin S ，Barut K ，Kasapcopur O ... -  《-》

Physicians' perspectives on the diagnosis and management of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome.

Manthiram K ，Li SC ，Hausmann JS ，Amarilyo G ，Barron K ，Kim H ，Nativ S ，Lionetti G ，Zeft A ，Goldsmith D ，Kimberlin D ，Edwards K ，Dedeoglu F ，Lapidus S ，Childhood Arthritis and Rheumatology Research Alliance (CARRA) PFAPA Subcommittee ... -  《-》