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.
Güngörer V, Ünal D, Çakan M, Ayduran S, Gül Ü , et al.
Clinical rheumatology •
Syndrome of undifferentiated recurrent fever (SURF) is an autoinflammatory disorder that is recognised in an increasing number of patients. In this study, we aimed to assess the data of SURF patients from the main reference centres in our country. Data for this retrospective multicentre observational cohort study were obtained from the records of SURF patients aged 0-18 years who were followed up in 10 pediatric rheumatology clinics in Türkiye between 2010 and June 2023. Patients with recurrent fever that could not be explained by periodic fever, aphthous stomatitis, pharyngitis and adenopathy (PFAPA) and hereditary recurrent fevers and had no other cause were included in the study. Of the 134 patients included in the study, 74 (55.2%) were male. The median age at diagnosis was 67 months. The most common symptom was abdominal pain in 98 (73.1%), arthralgia in 82 (61.2%), malaise in 77 (57.5%). The age at symptom onset was ≤ 5 years in 109 patients (81.3%). Pharyngitis was more common symptom in children aged ≤ 5 years (p = 0.008), headache, arthralgia, chest pain were more common findings in children > 5 years (p = 0.008, p = 0.032, p = 0.045). There were 113 patients receiving colchicine alone or in combination therapy and 74.3% of them achieved complete or partial remission. The presence of abdominal pain (p = 0.021, OR = 0.254) increased the remission rate with colchicine. SURF patients present with a wide range of clinical manifestations. Distinguishing between SURF and PFAPA is not concrete. Further omics studies will enlighten whether there is a true group of SURF. Key Points • SURF is an autoinflammatory disease that is becoming increasingly recognised. • The clinical manifestations of SURF are quite heterogeneous. • Colchicine and anti-IL-1 treatment is effective in most SURF patients. • It is controversial whether it should be called SURF or PFAPA-like syndrome, especially in children aged ≤ 5 years.
Aydın F, Kurt T, Sezer M, Tekgöz N, Ekici Tekin Z , et al.
Rheumatology international •
The diagnosis of Familial Mediterranean fever (FMF) based on clinical findings supported by genetic mutation. Recently, the new Eurofever/PRINTO classification criteria including genetic analysis were established. The aim of this study is to evaluate the performance of the new criteria in FMF patients with a single exon 10 mutation in childhood. The study group consisted of FMF patients who had a single exon 10 mutation in a referral center in Turkey. Patients with periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome were included as a control group. The medical charts of all patients were reviewed retrospectively. A total of 106 FMF patients (59 boys) were enrolled in the study group. The median age at first symptom was 5; the median age at diagnosis was 7 years. The mean follow-up was 33 ± 35.4 months. Majority of the patients (n = 58, 54.7%) had heterozygous M694V, 16 (15%) patients had M694V/E148Q and 13 (13.8%) patients had heterozygous M680I mutation. The sensitivity of the Yalcinkaya-Ozen criteria was 98.1% and it was 97.1% for the Eurofever/PRINTO classification criteria. The specificity of the new Eurofever/PRINTO classification criteria was 96.7% and it was 74.1% for the Yalcinkaya-Ozen criteria. The new Eurofever/PRINTO classification criteria have a good sensitivity as the Yalcinkaya-Ozen criteria in patients with a single exon 10 mutation. Additionaly, the new criteria have better specificity. It should be useful to apply the clinical only criteria where the carrier rate is high.