ArticlePediatric research2026
Perinatal and early childhood determinants of disease persistence in PFAPA.
Article in Pediatric research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundPeriodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis (PFAPA) is a common childhood autoinflammatory disease.
objectiveThis study investigated the influence of early-life factors on attack frequency and treatment resistance in children with PFAPA.
methodsEighty-one children with PFAPA (diagnosed April 2021-2024) were retrospectively evaluated and divided into persistent and non-persistent (self-limiting) groups. Persistent PFAPA was defined as a < 50% reduction in attack frequency since diagnosis, having undergone tonsillectomy for PFAPA, or experiencing ongoing attacks beyond 7 years of age.
resultsThe study included 81 PFAPA patients (female-to-male ratio 0.9; median age 76 months). The patients were divided into two groups: 28 persistent (34.6%) and 53 non-persistent (65.4%). Persistent patients had more frequent attacks (median 6 vs. 1 per year, p < 0.001) of shorter duration (median 3 vs. 4 days, p = 0.003), with less cervical lymphadenopathy (10.7% vs. 30.2%, p = 0.049) and abdominal pain (32.1% vs. 56.6%, p = 0.036). Preterm birth and pacifier use were less common in persistent patients (7.1% vs. 26.4%, p = 0.038; 25% vs. 52.8%, p = 0.016). In multivariate analysis, abdominal pain, preterm birth, and pacifier use independently predicted non-persistence, whereas colchicine use was non-significant.
conclusionEarly-life factors, including preterm birth and pacifier use, are associated with a self-limiting PFAPA phenotype. IMPACT: This study reveals that specific early-life factors-namely preterm birth and pacifier use-are independently associated with a milder, non-persistent PFAPA course. By identifying these perinatal and environmental influences, the research shifts the focus from purely clinical symptoms to the role of early immune maturation in disease trajectory. These findings provide clinicians with new tools to predict disease persistence, enabling more personalized management and better-informed parental counseling. The association between early-life exposures and PFAPA persistence offers a novel perspective on the pathogenesis of autoinflammatory conditions in children.
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