Benderlioğlu E, Efeoğlu Gülsoy G, Özçelik E, Çelikel Acar B
Pediatric research •
Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis (PFAPA) is a common childhood autoinflammatory disease. This study investigated the influence of early-life factors on attack frequency and treatment resistance in children with PFAPA. Eighty-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. The 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. Early-life factors, including preterm birth and pacifier use, are associated with a self-limiting PFAPA phenotype. 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.
Ömercioğlu E, Özçelik E, Akpınar F, Özdereli Z, Öztürk E , et al.
European journal of pediatrics •
Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome and familial Mediterranean fever (FMF) are the most common pediatric autoinflammatory syndromes, yet their developmental and psychosocial impacts during early childhood remain poorly understood. This cross-sectional study compared developmental and behavioral outcomes, parental mental health, and perceived child vulnerability in preschool-aged children diagnosed with PFAPA syndrome or FMF versus healthy controls. A total of 158 children aged 18-71 months (79 patients, 79 controls of similar age and sex) were recruited from a tertiary pediatric hospital in Turkiye. Development was evaluated using the Ages and Stages Questionnaire and Bayley Scales of Infant and Toddler Development, Third Edition. Behavioral functioning was assessed using the Child Behavior Checklist, while maternal depression, anxiety, and perception of child vulnerability were measured via the Patient Health Questionnaire-9, Beck Anxiety Inventory, and Child Vulnerability Scale. Children with periodic fever syndromes had significantly higher rates of developmental delay (p < 0.05) and lower cognitive, language, and motor scores than healthy peers (all p < 0.05). They also exhibited elevated internalizing and externalizing symptoms. Mothers of affected children reported higher perceptions of child vulnerability. Multivariable logistic regression identified male sex (OR 2.71, 95% CI 1.08-6.85), patient group status (OR 2.65, 95% CI 1.12-6.23), lack of preschool attendance (OR 6.58, 95% CI 2.26-19.19), and lower shared reading frequency (OR 0.76, 95% CI 0.65-0.89) as independent predictors of developmental delay. Among clinical factors, attack frequency was positively associated with internalizing problems.  Preschool children with PFAPA syndrome and FMF may be at increased risk for early developmental and behavioral difficulties. These findings support the need for routine screening and integrated care approaches that address both child development and caregiver-relate d factors. • PFAPA syndrome and FMF are the most common childhood periodic fever syndromes associated with stress and reduced quality of life in both children and their families. • Although inflammation and psychosocial stress are known to affect early development, their impact in these syndromes remains largely unexplored. • Preschool children with PFAPA syndrome and FMF are at increased risk for developmental and behavioral difficulties, along with elevated maternal perceptions of child vulnerability. • This is the first study to systematically evaluate early developmental and psychosocial outcomes in these syndromes, identifying clinical and caregiving factors associated with increased risk.
Öner N, Çelikel E, Tekin ZE, Güngörer V, Tekgöz N , et al.
Irish journal of medical science •
To evaluate the effect of vitamin D supplementation on the frequency and duration of attacks in patients of PFAPA syndrome with low vitamin D levels. This retrospective study comprised PFAPA patients with vitamin D deficiency/insufficiency between 2018 and 2023. The frequency and duration of PFAPA attacks before and after vitamin D supplementation were noted. Seventy-one patients were included. Of the 71 patients, 24 (33.8%) had vitamin D insufficiency, and 47 (66.2%) had vitamin D deficiency. In patients with vitamin D insufficiency, mean attack frequency and mean attack duration before vitamin D supplementation were 4.3 ± 1.9/year and 2.2 ± 1.6 days, respectively, while mean attack frequency and mean attack duration after vitamin D supplementation were 3.5 ± 2.7/year per year and 1.3 ± 0.9 days respectively (p = 0.2, p = 0.2, respectively). In patients with vitamin D deficiency, mean attack frequency and mean attack duration before vitamin D supplementation were 7.4 ± 2.1/year and 2.2 ± 1.6 days, respectively, while mean attack frequency and mean attack duration after vitamin D supplementation were 3.3 ± 2.4/year and 1.3 ± 0.9 days respectively (p < 0.01, p = 0.04, respectively). When the vitamin D level and the frequency of attacks were compared, the cut-off value of vitamin D was found to be 29.7 nmol/L. In PFAPA patients with low vitamin D levels, the frequency and duration of PFAPA attacks were reduced with vitamin D supplementation. Especially at vitamin D level cut-off > 29.7 nmol/L, the frequency of attacks reduced significantly.
