Amarilyo G, Rothman D, Manthiram K, Edwards KM, Li SC , et al.
Pediatric rheumatology online journal •
Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most common periodic fever syndrome in children. There is considerable heterogeneity in management strategies and a lack of evidence-based treatment guidelines. Consensus treatment plans (CTPs) are standardized treatment regimens that are derived based upon best available evidence and current treatment practices that are a way to enable comparative effectiveness studies to identify optimal therapy and are less costly to execute than randomized, double blind placebo controlled trials. The purpose of this project was to develop CTPs and response criteria for PFAPA. The CARRA PFAPA Working Group is composed of pediatric rheumatologists, infectious disease specialists, allergists/immunologists and otolaryngologists. An extensive literature review was conducted followed by a survey to assess physician practice patterns. This was followed by virtual and in-person meetings between 2014 and 2018. Nominal group technique (NGT) was employed to develop CTPs, as well as inclusion criteria for entry into future treatment studies, and response criteria. Consensus required 80% agreement. The PFAPA working group developed CTPs resulting in 4 different treatment arms: 1. Antipyretic, 2. Abortive (corticosteroids), 3. Prophylaxis (colchicine or cimetidine) and 4. Surgical (tonsillectomy). Consensus was obtained among CARRA members for those defining patient characteristics who qualify for participation in the CTP PFAPA study. The goal is for the CTPs developed by our group to lead to future comparative effectiveness studies that will generate evidence-driven therapeutic guidelines for this periodic inflammatory disease.
Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is considered the most common periodic fever syndrome of childhood. Although it was first described three decades ago, the pathogenesis has been poorly understood. Recent studies on the heritability and immunology of the disorder have begun to shed light into the mechanisms of this autoinflammatory disorder. This review will focus on the pathogenesis of PFAPA, especially as it pertains to the genetic susceptibility, tonsillar immunology, and the role of the microbiome. Recent literature provides insights into the heritability, potential genetic modifiers, and the immunologic and microbiological profile of the tonsils in this syndrome. Evidence is mounting that PFAPA is inherited as a complex genetic disease. Furthermore, tonsillectomy is curative in the majority of patients, including those who do not meet the complete clinical criteria for PFAPA. The tonsils in PFAPA patients may exhibit unique immunologic and microbiological features. The goal of this review is to outline these new developments.
Manthiram K, Li SC, Hausmann JS, Amarilyo G, Barron K , et al.
Rheumatology international •
To assess the practice patterns of pediatric rheumatology and infectious diseases subspecialists in the diagnosis and treatment of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome. An online survey assessing diagnostic and treatment approaches was sent to 424 members of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) and 980 members of the Pediatric Infectious Disease Society (PIDS). 277 physicians (123 from CARRA and 154 from PIDS representing 21% of the total membership) completed the survey. To diagnose PFAPA, most respondents agreed that patients must have the following features of the diagnostic criteria: stereotypical fever episodes (95%), asymptomatic intervals between episodes (93%), and normal growth and development (81%). However, 71% of the respondents did not require age of onset <5 years, 33% did not require regular intervals between episodes, and 79% did not require the concomitant signs of aphthous stomatitis, adenitis, or pharyngitis during episodes as long as episodes were regular. Over half (58%) considered episode resolution with steroids to be diagnostic of PFAPA. Corticosteroids, antipyretics, tonsillectomy, and cimetidine were the most commonly prescribed treatments, while steroids and tonsillectomy were most effective. Subspecialists in pediatric rheumatology and infectious diseases showed limited adherence to the complete published criteria for diagnosing PFAPA suggesting heterogeneity in the characteristics of patients diagnosed with the disorder. These findings emphasize the need to develop consensus diagnostic and treatment guidelines in well-characterized patient populations.