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.
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.
Kalayci F, Yigit M, Kuruc AI, Cevirici T, Celikel Acar B
Journal of paediatrics and child health •
This study aims to present the clinical characteristics of patients with PFAPA syndrome, and to compare the effects of corticosteroid usage, colchicine prophylaxis, and tonsillectomy on the frequency of attacks in patients with PFAPA syndrome. Patients aged between 6 months and 18 years presenting to our Paediatric Rheumatology clinic between 2017 and 2021 who were diagnosed with PFAPA syndrome and followed up for a minimum of 12 months were included in this study. The demographic and clinical characteristics of the patients, laboratory findings, attack durations, and treatments were recorded. Our study, comprised of 195 patients, included four groups: untreated (n = 58), corticosteroid (n = 43), colchicine (n = 62), and tonsillectomy (n = 32). There was no significant difference between the treatment groups in terms of attack frequencies before treatment initiation (p > 0.05). When attack frequencies before and after treatment initiation were observed, a decrease in attack frequency compared to the pre-treatment period was observed in the tonsillectomy group (from 12 to 3 attacks) (p < 0.001) and the colchicine group (from 12 attacks to 1 attack) (p < 0.001). It was noted that using steroids during three or more attacks increased attack frequency compared to the pre-treatment period (p < 0.0001). Tonsillectomy resulted in a more significant reduction in attack frequency compared to the colchicine group (p < 0.001). Using corticosteroids during an attack has been shown to effectively control attacks. However, the repeated use of corticosteroids increases the frequency of attacks. Colchicine prophylaxis leads to a reduction in attack frequency in the majority of cases. Tonsillectomy can successfully control the disease in most cases.
Küçükali B, Bayraktar EÖ, Yıldız Ç, Gönen S, Kutlar M , et al.
Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases •
The exact effects of MEFV variants on inflammation are still under investigation, and reports on variants of unknown significance, particularly the E148Q variant, have been conflicting. Therefore, this study aims to investigate patients exhibiting E148Q heterozygosity, focusing on diagnoses and disease courses to assist physicians in interpreting the variant. Data of pediatric patients presenting to the Pediatric Rheumatology clinic between November 2016 and September 2023, exhibiting only E148Q heterozygosity in MEFV gene analysis, were extracted. Patients who were lost before 9 months of follow-up have been excluded to ensure the completion of initial diagnostic tests and evaluations. Among the 119 patients with E148Q variant, the diagnoses were as follows: healthy, 51.3%; IgA vasculitis, 10.1%; Familial Mediterranean Fever (FMF), 7.6%; Periodic fever, Aphtous stomatitis, Pharyngitis, Adenitis (PFAPA), 6.7%; and other diagnoses, 19.3%. IgA vasculitis patients experienced articular, gastrointestinal, and renal involvement at rates of 91.7%, 58.3%, and 16.7%, respectively. Complete response, partial response, and no response to colchicine were 37.5%, 12.5%, and 50%, respectively, in PFAPA patients. All FMF patients responded to colchicine treatment resulting in reduced mean FMF episode counts in 6 months from 3.22 ± 0.92 to 0.56 ± 0.52. The E148Q variant may amplify inflammation and modify disease courses. Patients with the E148Q variant experiencing typical FMF episodes should receive colchicine, but clinicians should exercise caution regarding alternative diagnoses. Additionally, the E148Q variant may increase acute phase reactants and disease severity in IgA vasculitis. However, to reach definitive conclusions on its treatment-modifying role in PFAPA, universal diagnosis and treatment response criteria should be adopted.
Özaslan Z, Şen A, Uçar SA, Çakan M, Sanisoğlu B , et al.
European journal of pediatrics •
Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome (PFAPA) are the most common autoinflammatory syndromes in children. This study aimed to evaluate the clinical and laboratory parameters that may predict colchicine responsiveness.This retrospective, multicenter, cross-sectional study involved nine pediatric rheumatology centers from our country., The patients diagnosed with PFAPA were compared on the basis of their responses to colchicine. In the 806 (42.3% female 57.7% male) patients, the most common clinical findings were fever (100%), exudative tonsillitis (86.5%), pharyngitis (80.9%), and aphthous stomatitis (50.5%). The mean attack frequency was 13.5 ± 6.8 attacks per year lasting for a mean of 3.9 ± 1.1 days. Colchicine treatment was attempted in 519 (64.4%) patients, with 419 (80.7%) showing a favorable response. In patients who underwent MEFV gene analysis (70.8%), the most common variant was M694V heterozygous (16.8%). The presence of pharyngitis (p = 0.03, 95% CI 0.885 to 0.994), the presence of arthralgia (p = 0.04, 95% CI 0.169 to 0.958), and having more frequent attacks (p = 0.001, 95% CI 0.028 to 0.748) were found to be associated with colchicine unresponsiveness, whereas the carriage of the M694V variant (p = 0.001, 95% CI 0.065 to 0.242) was associated with colchicine responsiveness. This study identified the presence of pharyngitis, arthralgia, and increased attack frequency in patients with PFAPA as factors predicting colchicine unresponsiveness, whereas the carriage of the M694V variant emerged as a predictor of colchicine responsiveness. Predicting colchicine response at disease onset may facilitate a more effective management of PFAPA. • Colchicine treatment can be used in the prophylaxis of PFAPA disease. • Having the MEFV variant is the most commonly known factor in predicting response to colchicine. • The presence of pharyngitis or arthralgia, and more frequent attacks in PFAPA disease were found to be independently associated with colchicine unresponsiveness. • Carrying the M694V variant was identified as the sole factor predicting colchicine responsiveness.
Arslanoglu Aydin E, Baglan E, Bagrul Ä°, Kocamaz NG, Tuncez S , et al.
Postgraduate medicine •
Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome and familial Mediterranean fever (FMF) are autoinflammatory disorders typically characterized by recurrent fever attacks. These recurrent fever attacks can lead to depression and anxiety in mothers of these patients. This study aimed to compare the depression and anxiety levels in mothers of PFAPA and FMF patients. This study is a cross-sectional observational study. 48 mothers of children with FMF and 70 mothers of children with PFAPA participated in the study. Mothers in these two groups were compared in terms of anxiety and depression by using the validated Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI). Depression and anxiety scores of mothers were found to be similar in FMF and PFAPA groups. Moderate or high level of anxiety was seen in 32% of mothers of patients with PFAPA and 27% of mothers of patients with FMF. 23% of mothers of patients with PFAPA were evaluated as having moderate or severe depression, and 18% of mothers of patients with FMF were evaluated as having moderate depression. There was no statistically significant difference between the duration, frequency of attacks, recurrent hospitalizations, sociodemographic characteristics, and inventory scores. Depression and anxiety scores of mothers with children diagnosed with FMF and PFAPA are similar. These two diseases affect families psychosocially at similar levels. It is important to provide psychosocial support to families.